bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with physical activity following total knee arthroplasty for knee osteoarthritis: a longitudinal study
Authors: Fujita Remi , Ota Susumu , Yamamoto Yuri , Kataoka Akito , Warashina Hideki , Hayashi Takahiro , Matsunaga Naomichi , Sugiura Hideshi
Published: February 2024

Background

After total knee arthroplasty (TKA), patients’ physical activity (PA) levels at 6 months are lower than those of healthy subjects. Few studies have investigated the factors associated with PA at 6 months after TKA by objectively measuring preoperative and postoperative PA intensity using an accelerometer and knee function using a goniometer and dynamometer. The purpose of this study was to determine the factors associated with PA levels at 6 months after TKA based on objective data.

Methods

Eighty-two patients (mean [SD] age 74.5 [6.4] years) with moderate-to-severe knee osteoarthritis (OA) who were scheduled for TKA at the Nagoya Orthopaedic and Joint Replacement Clinic from July 2018 to July 2019 were enrolled in this longitudinal study. All patients underwent evaluations of knee function, including range-of-motion and knee-extension muscle strength; knee pain; performance in the timed up-and-go test; and accelerometer-measured PA both preoperatively and 6 months postoperatively. Factors associated with PA at 6 months after TKA were assessed using a hierarchical multiple linear regression analysis adjusted for age, sex, body mass index, and presence of diabetes mellitus.

Results

A higher average daily step count at 6 months after TKA was significantly associated with greater preoperative knee-extension muscle strength on the operated side (β = 0.155, p = 0.028) as well as a higher preoperative average daily step count (β = 0.834, p < 0.001). Furthermore, average daily time spent in moderate-to-vigorous-intensity PA postoperatively was significantly associated only with time spent in moderate-to-vigorous-intensity PA preoperatively (β = 0.723, p < 0.001).

Conclusion

These findings indicate that a higher preoperative daily step count and greater preoperative knee-extension muscle strength on the operated side may be associated with a higher daily step count at 6 months after TKA. Factors associated with PA differed by the PA intensity level. Rehabilitation and interventions for psychosocial factors before TKA beginning when mild knee OA first occurs are expected to lead to increased PA in TKA patients.
Inhibition of IL-17 signaling in macrophages underlies the anti-arthritic effects of halofuginone hydrobromide: Network pharmacology, molecular docking, and experimental validation
Authors: Zhu Junping , Wei Jiaming , Lin Ye , Tang Yuanyuan , Su Zhaoli , Li Liqing , Liu Bin , Cai Xiong
Published: February 2024

Background

Rheumatoid arthritis (RA) is a prevalent autoimmune disease marked by chronic synovitis as well as cartilage and bone destruction. Halofuginone hydrobromide (HF), a bioactive compound derived from the Chinese herbal plant Dichroa febrifuga Lour., has demonstrated substantial anti-arthritic effects in RA. Nevertheless, the molecular mechanisms responsible for the anti-RA effects of HF remain unclear.

Methods

This study employed a combination of network pharmacology, molecular docking, and experimental validation to investigate potential targets of HF in RA.

Results

Network pharmacology analyses identified 109 differentially expressed genes (DEGs) resulting from HF treatment in RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses unveiled a robust association between these DEGs and the IL-17 signaling pathway. Subsequently, a protein-protein interaction (PPI) network analysis revealed 10 core DEGs, that is, EGFR, MMP9, TLR4, ESR1, MMP2, PPARG, MAPK1, JAK2, STAT1, and MAPK8. Among them, MMP9 displayed the greatest binding energy for HF. In an in vitro assay, HF significantly inhibited the activity of inflammatory macrophages, and regulated the IL-17 signaling pathway by decreasing the levels of IL-17 C, p-NF-κB, and MMP9.

Conclusion

In summary, these findings suggest that HF has the potential to inhibit the activation of inflammatory macrophages through its regulation of the IL-17 signaling pathway, underscoring its potential in the suppression of immune-mediated inflammation in RA.
Factors influencing the use of natural health products, in particular for concentration and cognition in Germany
Authors: Wolf Miriam , Emberger-Klein Agnes , Menrad Klaus
Published: February 2024

Background

Natural health products (NHP) are an important part of the healthcare system. They are mainly non-prescription and sold over the counter, which requires active decision making by the consumer. Within the framework of the Complementary and Alternative Healthcare Model, this study aims to identify factors that influence NHP usage, in particular related to concentration and cognition (CC), a topic that concerns all ages and social classes within the population.

Methods

Data were collected by means of a representative online survey (n = 1,707) in Germany in April 2022. Three user groups were defined: NHPCC users, who used NHP for CC (12 month prevalence); nCC-NHP users, who used NHP but not for CC indications (12 month prevalence); and past NHP users, who have used NHP but not within the previous 12 months. Independent influencing variables were categorized into predisposing, enabling, need, and health service use factors. Data were analyzed with descriptive statistics, inferential statistics, and binary logistic regression models to compare NHPCC users to nCC-NHP users (model 1) and to past NHP users (model 2).

Results

A higher share of NHPCC and nCC-NHP users compared to past NHP users were women, self-medicated with NHP, and used information about NHP provided by health professionals or on product. Their openness-to-change value orientation was more pronounced than of past users. Compared to nCC-NHP and past NHP users, the probability of being an NHPCC user increased if an individual had more difficulties in daily attention and memory performance, made use of health professionals and literature to seek information about NHP, and used NHP for health support and illness prevention. Additionally, a female gender, NHP self-medication, and having higher values of self-transcendence were significant indicators for NHPCC usage compared to past NHP usage.

Conclusion

NHP manufacturers, health professionals, and policymakers should be aware of the factors that lead to NHP consumption decisions and consider them in the development and optimization of healthcare strategies as well as in the marketing and communication strategies of companies producing NHP, in particular for CC. The current study can contribute to characterizing the target groups and to defining the aims and communication channels of such campaigns.
Evaluating a peer-to-peer health education program in Australian public housing communities during the COVID-19 pandemic
Authors: Oliver Jane , Ferdinand Angeline , Hussein Awil , Hussein Ruqiyo , Kaufman Jessica , Edler Peta , Allard Nicole , Danchin Margie , Gibney Katherine B.
Published: February 2024

Background

The cohealth Health Concierge program operated in Melbourne, Australia from July 2020 to 30 June 2022. It provided peer-to-peer support to culturally and linguistically diverse residents of high-rise public housing. During this time, the COVID-19 public health response changed frequently and included movement restriction, testing and vaccination. We conducted a mixed-methods evaluation to determine the Health Concierge program’s impact on residents’ engagement with health services and public health activities.

Methods

The evaluation, informed by a Project Reference Group, used the RE-AIM framework. We analysed data from 20,901 routinely collected forms describing interactions between Concierges and residents from August 2021 to May 2022. Additional evaluation-specific data were collected between March and May 2022 in four housing estates; we surveyed 301 residents and conducted 32 interviews with residents, Concierges and program stakeholders.

Results

Concierges promoted COVID-safe behaviours; linked residents with support, testing and vaccination services; and disseminated up-to-date information. Of the 20,901 recorded interactions, 8,872 (42%) included Concierges providing support around COVID-19 vaccination. Most surveyed residents (191/301, 63%) reported speaking with a Concierge in the previous six months. The self-reported two-dose COVID-19 vaccine uptake was 94% (283/301). Some residents described having meaningful, appreciated conversations with Concierges, and some described superficial interactions. While residents initially welcomed the program, many felt it failed to evolve. Poorly defined management and hiring criteria led to variable program implementation. A need for bicultural workers to continue linking residents with services was discussed.

Conclusions

Concierges’ impact on residents may have contributed to high community uptake of COVID-19 testing and vaccination, and had benefits beyond the COVID-19 remit. We recommend the program be revised and continued to inform further preparedness planning and support service access generally. Program models such as this have potential to inform and reassure high-risk communities during a pandemic. In addition, such programs can help overcome vaccine hesitancy and promote protective health behaviours, regardless of whether a pandemic is currently occurring. Ensuring these programs remain responsive to the changing needs of end-users needs over time is imperative.
Functional characterization of NBS-LRR genes reveals an NBS-LRR gene that mediates resistance against Fusarium wilt
Authors: Cao Yunpeng , Mo Wanzhen , Li Yanli , Xiong Yao , Wang Han , Zhang Yingjie , Lin Mengfei , Zhang Lin , Li Xiaoxu
Published: February 2024

Background

Most disease resistance (R) genes in plants encode proteins that contain leucine-rich-repeat (LRR) and nucleotide-binding site (NBS) domains, which belong to the NBS-LRR family. The sequenced genomes of Fusarium wilt-susceptible Vernicia fordii and its resistant counterpart, Vernicia montana, offer significant resources for the functional characterization and discovery of novel NBS-LRR genes in tung tree.

Results

Here, we identified 239 NBS-LRR genes across two tung tree genomes: 90 in V. fordii and 149 in V. montana. Five VmNBS-LRR paralogous were predicted in V. montana, and 43 orthologous were detected between V. fordii and V. montana. The orthologous gene pair Vf11G0978-Vm019719 exhibited distinct expression patterns in V. fordii and V. montana: Vf11G0978 showed downregulated expression in V. fordii, while its orthologous gene Vm019719 demonstrated upregulated expression in V. montana, indicating that this pair may be responsible for the resistance to Fusarium wilt in V. montana. Vm019719 from V. montana, activated by VmWRKY64, was shown to confer resistance to Fusarium wilt in V. montana by a virus-induced gene silencing (VIGS) experiment. However, in the susceptible V. fordii, its allelic counterpart, Vf11G0978, exhibited an ineffective defense response, attributed to a deletion in the promoter’s W-box element.

Conclusions

This study provides the first systematic analysis of NBS-LRR genes in the tung tree and identifies a candidate gene that can be utilized for marker-assisted breeding to control Fusarium wilt in V. fordii.
Evolution of ancient satellite DNAs in extant alligators and caimans (Crocodylia, Reptilia)
Authors: Sales-Oliveira Vanessa C. , dos Santos Rodrigo Zeni , Goes Caio Augusto Gomes , Calegari Rodrigo Milan , Garrido-Ramos Manuel A. , Altmanová Marie , Ezaz Tariq , Liehr Thomas , Porto-Foresti Fabio , Utsunomia Ricardo , Cioffi Marcelo B.
Published: February 2024

Background

Crocodilians are one of the oldest extant vertebrate lineages, exhibiting a combination of evolutionary success and morphological resilience that has persisted throughout the history of life on Earth. This ability to endure over such a long geological time span is of great evolutionary importance. Here, we have utilized the combination of genomic and chromosomal data to identify and compare the full catalogs of satellite DNA families (satDNAs, i.e., the satellitomes) of 5 out of the 8 extant Alligatoridae species. As crocodilian genomes reveal ancestral patterns of evolution, by employing this multispecies data collection, we can investigate and assess how satDNA families evolve over time.

Results

Alligators and caimans displayed a small number of satDNA families, ranging from 3 to 13 satDNAs in A. sinensis and C. latirostris, respectively. Together with little variation both within and between species it highlighted long-term conservation of satDNA elements throughout evolution. Furthermore, we traced the origin of the ancestral forms of all satDNAs belonging to the common ancestor of Caimaninae and Alligatorinae. Fluorescence in situ experiments showed distinct hybridization patterns for identical orthologous satDNAs, indicating their dynamic genomic placement.

Conclusions

Alligators and caimans possess one of the smallest satDNA libraries ever reported, comprising only four sets of satDNAs that are shared by all species. Besides, our findings indicated limited intraspecific variation in satellite DNA, suggesting that the majority of new satellite sequences likely evolved from pre-existing ones.
Membranes are functionalized by a proteolipid code
Authors: Kervin Troy A. , Overduin Michael
Published: February 2024

Membranes are protein and lipid structures that surround cells and other biological compartments. We present a conceptual model wherein all membranes are organized into structural and functional zones. The assembly of zones such as receptor clusters, protein-coated pits, lamellipodia, cell junctions, and membrane fusion sites is explained to occur through a protein-lipid code. This challenges the theory that lipids sort proteins after forming stable membrane subregions independently of proteins.
The cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafish
Authors: Veloso Alexandra , Bleuart Anouk , Conrard Louise , Orban Tanguy , Bruyr Jonathan , Cabochette Pauline , Germano Raoul F. V. , Schevenels Giel , Bernard Alice , Zindy Egor , Demeyer Sofie , Vanhollebeke Benoit , Dequiedt Franck , Martin Maud
Published: February 2024

Background

Lymphangiogenesis, the formation of lymphatic vessels, is tightly linked to the development of the venous vasculature, both at the cellular and molecular levels. Here, we identify a novel role for Sorbs1, the founding member of the SoHo family of cytoskeleton adaptor proteins, in vascular and lymphatic development in the zebrafish.

Results

We show that Sorbs1 is required for secondary sprouting and emergence of several vascular structures specifically derived from the axial vein. Most notably, formation of the precursor parachordal lymphatic structures is affected in sorbs1 mutant embryos, severely impacting the establishment of the trunk lymphatic vessel network. Interestingly, we show that Sorbs1 interacts with the BMP pathway and could function outside of Vegfc signaling. Mechanistically, Sorbs1 controls FAK/Src signaling and subsequently impacts on the cytoskeleton processes regulated by Rac1 and RhoA GTPases. Inactivation of Sorbs1 altered cell-extracellular matrix (ECM) contacts rearrangement and cytoskeleton dynamics, leading to specific defects in endothelial cell migratory and adhesive properties.

Conclusions

Overall, using in vitro and in vivo assays, we identify Sorbs1 as an important regulator of venous and lymphatic angiogenesis independently of the Vegfc signaling axis. These results provide a better understanding of the complexity found within context-specific vascular and lymphatic development.
Mesenchymal stromal cells plus basiliximab improve the response of steroid-refractory acute graft-versus-host disease as a second-line therapy: a multicentre, randomized, controlled trial
Authors: Fu Haixia , Sun Xueyan , Lin Ren , Wang Yu , Xuan Li , Yao Han , Zhang Yuanyuan , Mo Xiaodong , lv Meng , Zheng Fengmei , Kong Jun , Wang Fengrong , Yan Chenhua , Han Tingting , Chen Huan , Chen Yao , Tang Feifei , Sun Yuqian , Chen Yuhong , Xu Lanping , Liu Kaiyan , Zhang Xi , Liu Qifa , Huang Xiaojun , Zhang Xiaohui
Published: February 2024

Background

For patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD), effective second-line regimens are urgently needed. Mesenchymal stromal cells (MSCs) have been used as salvage regimens for SR-aGVHD in the past. However, clinical trials and an overall understanding of the molecular mechanisms of MSCs combined with basiliximab for SR-aGVHD are limited, especially in haploidentical haemopoietic stem cell transplantation (HID HSCT).

Methods

The primary endpoint of this multicentre, randomized, controlled trial was the 4-week complete response (CR) rate of SR-aGVHD. A total of 130 patients with SR-aGVHD were assigned in a 1:1 randomization schedule to the MSC group (receiving basiliximab plus MSCs) or control group (receiving basiliximab alone) (NCT04738981).

Results

Most enrolled patients (96.2%) received HID HSCT. The 4-week CR rate of SR-aGVHD in the MSC group was obviously better than that in the control group (83.1% vs. 55.4%, P = 0.001). However, for the overall response rates at week 4, the two groups were comparable. More patients in the control group used ≥ 6 doses of basiliximab (4.6% vs. 20%, P = 0.008). We collected blood samples from 19 consecutive patients and evaluated MSC-derived immunosuppressive cytokines, including HO1, GAL1, GAL9, TNFIA6, PGE2, PDL1, TGF-β and HGF. Compared to the levels before MSC infusion, the HO1 (P = 0.0072) and TGF-β (P = 0.0243) levels increased significantly 1 day after MSC infusion. At 7 days after MSC infusion, the levels of HO1, GAL1, TNFIA6 and TGF-β tended to increase; however, the differences were not statistically significant. Although the 52-week cumulative incidence of cGVHD in the MSC group was comparable to that in the control group, fewer patients in the MSC group developed cGVHD involving ≥3 organs (14.3% vs. 43.6%, P = 0.006). MSCs were well tolerated, no infusion-related adverse events (AEs) occurred and other AEs were also comparable between the two groups. However, patients with malignant haematological diseases in the MSC group had a higher 52-week disease-free survival rate than those in the control group (84.8% vs. 65.9%, P = 0.031).

Conclusions

For SR-aGVHD after allo-HSCT, especially HID HSCT, the combination of MSCs and basiliximab as the second-line therapy led to significantly better 4-week CR rates than basiliximab alone. The addition of MSCs not only did not increase toxicity but also provided a survival benefit.
An observational study demonstrates human-adapted Staphylococcus aureus strains have a higher frequency of antibiotic resistance compared to cattle-adapted strains isolated from dairy farms making farmstead cheese
Authors: Chakrawarti Ashma , Casey Christine L. , Burk Ariela , Mugabi Robert , Ochoa Amanda , Barlow John W.
Published: February 2024

Background

Staphylococcus aureus is a multi-host zoonotic pathogen causing human and livestock diseases. Dairy farms that make artisan cheese have distinctive concerns for S. aureus control. Antimicrobial-resistant (AMR) S. aureus is a public and animal health concern. There is a need to study the population structure of AMR S. aureus at the human-animal interface and understand the path of zoonotic transmission. This cross-sectional observational study aimed to assess the genetic diversity and AMR patterns of S. aureus isolated from cattle and humans on conventional and organic Vermont dairy farms that produce and sell farmstead cheese.

Results

A convenience sample of 19 dairy farms in Vermont was enrolled, and 160 S. aureus isolates were collected from cow quarter milk (CQM), bulk tank milk (BTM), human-hand and -nasal swabs. After deduplication, 89 isolates were used for the analysis. Sequence types (STs) were determined by multilocus sequence typing and cataloged to the PubMLST database. Nine defined and five novel STs were identified. For BTM and CQM samples, six STs were identified within cow-adapted CC97 and CC151. Two human-adapted STs were isolated from BTM and CQM. Seven human-adapted clonal complexes with eight STs were identified from human samples. One cow-adapted ST was isolated from a human. Antimicrobial susceptibility of the isolates was tested using disc diffusion and broth microdilution methods. Approximately 27% of the isolates were beta-lactam resistant and blaZ gene-positive. S. aureus isolates from human swabs were more likely to carry blaZ compared to isolates from CQM or BTM. S. aureus isolated from cows and humans on the same farm belonged to different STs.

Conclusion

Humans were more likely to carry beta-lactam-resistant S. aureus compared to cows, and on organic farms only human-adapted blaZ positive STs were isolated from BTM. Moreover, we identified potential spillover events of S. aureus sequence types between host species. The presence of penicillin-resistant-human-adapted S. aureus on both organic and conventional dairy farms highlights a “One Health” concern at the junction of public and animal health requiring further surveillance.
How using light touch immersion research revealed important insights into the lack of progress in malaria elimination in Eastern Indonesia
Authors: Jupp Dee , Ayuandini Sherria , Tobing Frisca , Halim Denny , Kenangalem Enny , Sumiwi Maria E. , Prameswari Hellen D. , Theodora Minerva , Susanto Hermawan , Dewi Riskha T. P. , Supriyanto Dedy , Kurnia Bayu , Shetye Mrunal , Ndoen Ermi , Onishi Yuka
Published: February 2024

Background

By 2022, the Government of Indonesia had successfully eliminated malaria in 389 out of 514 districts but continues to face a challenge in Eastern Indonesia where 95% of the total 2021 malaria cases were reported from Papua, West Papua and Nusa Tenggara Timur provinces. There is an increased recognition that malaria elimination will require a better understanding of the human behavioural factors hindering malaria prevention and treatment, informed by local context and local practice.

Methods

This research used a light-touch immersion research approach. Field researchers lived in communities over several days to gather data through informal conversations, group-based discussions using visual tools, participant observation and direct experience. The study was conducted in four high malaria endemic areas in Papua, West Papua, and Sumba Islands in Nusa Tenggara Timur.

Results

The research highlights how people’s perception of malaria has changed since the introduction of effective treatment which, in turn, has contributed to a casual attitude towards early testing and adherence to malaria treatment. It also confirms that people rarely accept there is a link between mosquitoes and malaria based on their experience but nevertheless take precautions against the annoyance of mosquitoes. There is widespread recognition that babies and small children, elderly and incomers are more likely to be seriously affected by malaria and separately, more troubled by mosquitoes than indigenous adult populations. This is primarily explained by acclimatization and strong immune systems among the latter.

Conclusions

Using immersion research enabled behaviour research within a naturalistic setting, which in turn enabled experiential-led analysis of findings and revealed previously unrecognized insights into attitudes towards malaria in Eastern Indonesia. The research provides explanations of people’s lack of motivation to consistently use bed nets, seek early diagnosis or complete courses of treatment. The felt concern for the wellbeing of vulnerable populations highlighted during light touch immersion provides an entry point for future social behaviour change communication interventions. Rather than trying to explain transmission to people who deny this connection, the research concludes that it may be better to focus separately on the two problems of malaria and mosquitoes (especially for vulnerable groups) thereby resonating with local people’s own experience and felt concerns.
Aligning the planning, development, and implementation of complex interventions to local contexts with an equity focus: application of the PRISM/RE-AIM Framework
Authors: Jolles Monica Pérez , Fort Meredith P. , Glasgow Russell E.
Published: February 2024

For the fields of implementation science and health equity, understanding and being responsive to local contexts is of utmost importance to better inform the development, implementation, and evaluation of healthcare and public health interventions to increase their uptake and sustainment. Contexts are multi-level and include political, historical, economic, and social factors that influence health, as well as organizational characteristics, reflecting the richness of members’ views, resources, values, and needs. Poor alignment between solutions and those contextual characteristics could have an impact on inequities. The PRISM (Practical Robust Implementation and Sustainability Model) is a context-based implementation science framework that incorporates RE-AIM outcomes (Reach, Effectiveness, Adoption, Implementation, Maintenance) and offers guidance to researchers, practitioners, and their patient and community partners on how to conceptualize, assess, and address contextual domains with a focus on health equity. Drawing from systems thinking, participatory engagement, and health equity principles, this commentary expands on previous work to 1) offer a novel perspective on how to align an intervention’s core functions and forms with the PRISM’s contextual domains, and 2) foster an ongoing and iterative engagement process with diverse partners throughout the research and practice process using a co-creation approach. We recommend intervention-to-context alignment through iterative cycles. To that end, we present the RE-AIM Framework’s ‘outcomes cascade’ to illustrate touch points of opportunity and gaps within and across each of the five RE-AIM outcomes to illustrate ‘where things go wrong’. We present a case study to illustrate and offer recommendations for research and practice efforts to increase contextual responsiveness, and enhance alignment with context before, during, and after implementation efforts and to ensure equity is being addressed. We strive to make a conceptual contribution to advance the field of pragmatic research and implementation of evidence-based practices through the application of the contextually-based PRISM framework with a focus on health equity.
Gender health gap pre- and post-joint arthroplasty: identifying affected patient-reported health domains
Authors: Steinbeck Viktoria , Bischof Anja Yvonne , Schöner Lukas , Langenberger Benedikt , Kuklinski David , Geissler Alexander , Pross Christoph , Busse Reinhard
Published: February 2024

Background

As patient-reported outcomes (PROs) gain prominence in hip and knee arthroplasty (HA and KA), studies indicate PRO variations between genders. Research on the specific health domains particularly impacted is lacking. Hence, we aim to quantify the gender health gap in PROs for HA/KA patients, differentiating between general health, health-related quality of life (HrQoL), physical functioning, pain, fatigue, and depression.

Methods

The study included 3,693 HA patients (1,627 men, 2,066 women) and 3,110 KA patients (1,430 men, 1,680 women) receiving surgery between 2020 to 2021 in nine German hospitals, followed up until March 2022. Questionnaires used were: EQ-VAS, EQ-5D-5L, HOOS-PS, KOOS-PS, PROMIS-F-SF, PROMIS-D-SF, and a joint-specific numeric pain scale. PROs at admission, discharge, 12-months post-surgery, and the change from admission to 12-months (PRO-improvement) were compared by gender, tested for differences, and assessed using multivariate linear regressions. To enable comparability, PROs were transformed into z-scores (standard deviations from the mean).

Results

Observed differences between genders were small in all health domains and differences reduced over time. Men reported significantly better health versus women pre-HA (KA), with a difference of 0.252 (0.224) standard deviations from the mean for pain, 0.353 (0.243) for fatigue (PROMIS-F-SF), 0.327 (0.310) for depression (PROMIS-D-SF), 0.336 (0.273) for functionality (H/KOOS-PS), 0.177 (0.186) for general health (EQ-VAS) and 0.266 (0.196) for HrQoL (EQ-5D-5L). At discharge, the gender health gap reduced and even disappeared for some health dimensions since women improved in health to a greater extent than men. No gender health gap was observed in most PRO-improvements and at month 12.

Conclusions

Men experiencing slightly better health than women in all health dimensions before surgery while experiencing similar health benefits 12-months post-surgery, might be an indicator of men receiving surgery inappropriately early, women unnecessarily late or both. As studies often investigate the PRO-improvement, they miss pre-surgery gender differences, which could be an important target for improvement initiatives in patient-centric care. Moreover, future research on cutoffs for meaningful between-group PRO differences per measurement time would aid the interpretation of gender health disparities.

Trial registration

German Register for Clinical Trials, DRKS00019916, 26 November 2019.
Minicells as an Escherichia coli mechanism for the accumulation and disposal of fluorescent cadmium sulphide nanoparticles
Authors: Valenzuela-Ibaceta Felipe , Torres-Olea Nicolás , Ramos-Zúñiga Javiera , Dietz-Vargas Claudio , Navarro Claudio A. , Pérez-Donoso José M.
Published: February 2024

Background

Bacterial biosynthesis of fluorescent nanoparticles or quantum dots (QDs) has emerged as a unique mechanism for heavy metal tolerance. However, the physiological pathways governing the removal of QDs from bacterial cells remains elusive. This study investigates the role of minicells, previously identified as a means of eliminating damaged proteins and enhancing bacterial resistance to stress. Building on our prior work, which unveiled the formation of minicells during cadmium QDs biosynthesis in Escherichia coli, we hypothesize that minicells serve as a mechanism for the accumulation and detoxification of QDs in bacterial cells.

Results

Intracellular biosynthesis of CdS QDs was performed in E. coli mutants ΔminC and ΔminCDE, known for their minicell-producing capabilities. Fluorescence microscopy analysis demonstrated that the generated minicells exhibited fluorescence emission, indicative of QD loading. Transmission electron microscopy (TEM) confirmed the presence of nanoparticles in minicells, while energy dispersive spectroscopy (EDS) revealed the coexistence of cadmium and sulfur. Cadmium quantification through flame atomic absorption spectrometry (FAAS) demonstrated that minicells accumulated a higher cadmium content compared to rod cells. Moreover, fluorescence intensity analysis suggested that minicells accumulated a greater quantity of fluorescent nanoparticles, underscoring their efficacy in QD removal. Biosynthesis dynamics in minicell-producing strains indicated that biosynthesized QDs maintained high fluorescence intensity even during prolonged biosynthesis times, suggesting continuous QD clearance in minicells.

Conclusions

These findings support a model wherein E. coli utilizes minicells for the accumulation and removal of nanoparticles, highlighting their physiological role in eliminating harmful elements and maintaining cellular fitness. Additionally, this biosynthesis system presents an opportunity for generating minicell-coated nanoparticles with enhanced biocompatibility for diverse applications.

Graphical Abstract
“They make it too hard and too many hoops to jump”: system and organizational barriers to drug treatment during epidemic rates of opioid overdose
Authors: Dickson-Gomez Julia , Krechel Sarah , Ohlrich Jessica , Montaque Helena Danielle Green , Weeks Margaret , Li Jianghong , Havens Jennifer , Spector Antoinette
Published: February 2024

Introduction

The United States is currently facing an opioid overdose crisis. Research suggests that multiple interventions are needed to reduce overdose deaths including increasing access and retention to medications to treat opioid use disorders (MOUD, i.e., methadone, buprenorphine, and naltrexone) and increasing the distribution and use of naloxone, a medication that can reverse the respiratory depression that occurs during opioid overdoses. However, barriers to MOUD initiation and retention persist and discontinuations of MOUD carry a heightened risk of overdose. Many times, MOUD is not sought as a first line of treatment by people with opioid use disorder (OUD), many of whom seek treatment from medically managed withdrawal (detox) programs. Among those who do initiate MOUD, retention is generally low. The present study examines the treatment experiences of people who use opioids in three states, Connecticut, Kentucky, and Wisconsin.

Methods

We conducted in-depth interviews with people who use opioids in a rural, urban, and suburban area of three states: Connecticut, Kentucky and Wisconsin. Data analysis was collaborative and key themes were identified through multiple readings, coding of transcripts and discussion with all research team members.

Results

Results reveal a number of systemic issues that reduce the likelihood that people initiate and are retained on MOUD including the ubiquity of detox as a first step in drug treatment, abstinence requirements and requiring patients to attend group treatment. MOUD-related stigma was a significant factor in the kinds of treatment participants chose and their experiences in treatment.

Conclusions

Interventions to reduce MOUD stigma are needed to encourage MOUD as a first course of treatment. Eliminating abstinence-based rules for MOUD treatment may improve treatment retention and decrease overdose risk.
Structural stigma within inpatient care for people who inject drugs: implications for harm reduction
Authors: Rehman Maham , Chapman Leigh , Liu Lisa , Calvert Sara , Sukhera Javeed
Published: February 2024

Background

 Individuals suffering with addiction have historically experienced disproportionally high levels of stigma. The process of inpatient care for those with substance abuse disorder (SUD) is multifaceted, shaped by the interplay of human interactions within the healthcare team and overarching structural factors like policy. While existing literature predominantly addresses personal and interpersonal stigma, the influence of structural stigma on care delivery practices remains understudied. Our research aims to investigate the impact of structural stigma on care processes for individuals with SUD admitted to acute medicine units.

Methods

 We conducted a secondary analysis of observation notes and interview transcripts utilizing an analytic framework related to structural stigma adapted from previous research. Data was collected from June 2019 to January 2020 in 2 hospitals. 81 participants consented to observation and 25 to interviews. Interviews were conducted with patients (n = 8), healthcare staff (n = 16), and caregivers (n = 1).

Results

 Each aspect of care for people with SUD is adversely influenced by structural forms of stigma. There was evidence of a gap in accessing care and time pressures which deteriorated care processes. Structural stigma also manifested in the physical spaces designed for care and the lack of adequate resources available for mental health and addictions care. We found that structural stigma perpetuated other forms of implicit and explicit stigma.

Conclusions

 Structural stigma and other forms of stigma are interconnected. Improving care for people with SUD in hospital settings may require addressing structural forms of stigma such as how physical spaces are designed and how mental healthcare is integrated with physical healthcare within inpatient settings.
Associations of multimorbidity with body pain, sleep duration, and depression among middle-aged and older adults in China
Authors: Ye Xin , Wang Xinfeng
Published: February 2024

Background

Multimorbidity, body pain, sleep disturbance, and depression are major clinical and public health challenges. This paper aimed to examine the associations of multimorbidity with body pain, sleep duration, and depression; and whether the associations varied by socioeconomic status.

Methods

Data was derived from four waves of the nationally representative China Health and Retirement Longitudinal Study (CHARLS), including participants aged 45 years and older in 2011. 12 physical non-communicable diseases and 1 mental chronic disease were used to measure multimorbidity. Educational attainment and annual per-capita household consumption expenditure were employed as proxies for socioeconomic status.

Results

Of the 16,931 participants aged 45 + years old, the proportion of people with multimorbidity was 37.87% at baseline. The number of multimorbidity increased with older age and higher socioeconomic status. Multimorbidity was associated with more body pain (incidence rate ratio (IRR) = 1.53, 95% CI = 1.45–1.61), and decreased sleep duration (β = -0.26, 95% CI = -0.36–-0.15). Furthermore, multimorbidity was associated with increased depression risks (odds ratio (OR) = 1.54, 95% CI = 1.44–1.64, adjusted for sociodemographic variables), with the mediating effects of the number of body pain and sleep duration. The associations between multimorbidity and depression persisted among different socioeconomic groups.

Conclusions

Multimorbidity was associated with increased body pain, decreased sleep duration, and further led to increased depression risks. It is necessary to pay attention to the multimorbidity of middle-aged and older adults, relieve their body pain, guarantee sufficient sleep, so as to reduce depression risks.
E-cadherin variants associated with oral facial clefts trigger aberrant cell motility in a REG1A-dependent manner
Authors: Pereira Joana , Melo Soraia , Ferreira Rui M. , Carneiro Patrícia , Yang Vítor , Maia André F. , Carvalho João , Figueiredo Ceu , Machado José Carlos , Morais-de-Sá Eurico , Seruca Raquel , Figueiredo Joana
Published: February 2024

Background

Germline mutations of E-cadherin contribute to hereditary diffuse gastric cancer (HDGC) and congenital malformations, such as oral facial clefts (OFC). However, the molecular mechanisms through which E-cadherin loss-of-function triggers distinct clinical outcomes remain unknown. We postulate that E-cadherin-mediated disorders result from abnormal interactions with the extracellular matrix and consequent aberrant intracellular signalling, affecting the coordination of cell migration.

Methods

Herein, we developed in vivo and in vitro models of E-cadherin mutants associated with either OFC or HDGC. Using a Drosophila approach, we addressed the impact of the different variants in cell morphology and migration ability. By combining gap closure migration assays and time-lapse microscopy, we further investigated the migration pattern of cells expressing OFC or HDGC variants. The adhesion profile of the variants was evaluated using high-throughput ECM arrays, whereas RNA sequencing technology was explored for identification of genes involved in aberrant cell motility.

Results

We have demonstrated that cells expressing OFC variants exhibit an excessive motility performance and irregular leading edges, which prevent the coordinated movement of the epithelial monolayer. Importantly, we found that OFC variants promote cell adhesion to a wider variety of extracellular matrices than HDGC variants, suggesting higher plasticity in response to different microenvironments. We unveiled a distinct transcriptomic profile in the OFC setting and pinpointed REG1A as a putative regulator of this outcome. Consistent with this, specific RNAi-mediated inhibition of REG1A shifted the migration pattern of OFC expressing cells, leading to slower wound closure with coordinated leading edges.

Conclusions

We provide evidence that E-cadherin variants associated with OFC activate aberrant signalling pathways that support dynamic rearrangements of cells towards improved adaptability to the microenvironment. This proficiency results in abnormal tissue shaping and movement, possibly underlying the development of orofacial malformations.

Graphical Abstract
A comprehensive interventional program to improve the sexual function of women with endometriosis: a mixed-methods protocol study
Authors: Sarvestani Maryam Heidari , Noroozi Mahnaz , Hashemi Maryam , Mostafavi Firoozeh
Published: February 2024

Background

Endometriosis is a chronic disease affecting 6–10% of women worldwide. Sexual dysfunction has been reported in a significant percentage of these patients. Thus, the present study will be conducted to design, implement, and determine the effectiveness of an interventional program to improve the sexual function of women with endometriosis.

Materials and methods

This mixed-methods study will be carried out in three phases with a sequential exploratory approach. In the first phase (qualitative study) participants will be selected by purposive sampling in Isfahan, Iran. The data will be collected through in-depth interviews and field notes and analyzed using conventional content analysis. The interventional program will be designed in the second phase based on the results of the qualitative study and literature review and using the Delphi method and panel of experts. The interventional program will be implemented at the individual level in the third phase to investigate its effect on improving women’s sexual function. This phase includes quasi-experimental research, in which the pre- and post-intervention data will be collected from the intervention and control groups using the FSFI questionnaire and analyzed by descriptive and inferential statistical methods. Ultimately, a suitable interventional program will be presented by combining the data obtained in the qualitative and quantitative phases of the research.

Conclusion

Conducting the present study, along with the design and implementation of an appropriate, native, and culturally sensitive interventional program, can contribute to improving the sexual function of women with endometriosis and enhancing the quality of sexual relations between couples.
Molecular epidemiology and phylogenetic analysis of feline calicivirus in Kunshan, China
Authors: Kim Semin , Cheng Yixi , Fang Zhenkun , Liu Xinyue , Zhongqi Qiu , Weidong Yu , Yilmaz Aysun , Yilmaz Huseyin , Umar Sajid
Published: February 2024

Feline calicivirus (FCV) is a highly contagious virus in cats, which typically causes respiratory tract and oral infections. Despite vaccination against FCV being a regular practice in China, new FCV cases still occur. Antigenic diversity of FCV hinders the effective control by vaccination. This is first report which aims to investigate the molecular epidemiology and molecular characteristics of FCV in Kunshan, China. The nasopharyngeal swabs were collected from cats showing variable clinical signs from different animal clinics in Kunshan from 2022 to 2023. Preliminary detection and sequencing of the FCV capsid gene were performed to study genetic diversity and evolutionary characteristics. FCV-RNA was identified in 52 (26%) of the samples using RT-PCR. A significant association was found between FCV-positive detection rate, age, gender, vaccination status and living environment, while a non-significant association was found with breed of cats. Nucleotide analysis revealed two genotypes, GI and GII. GII predominated in Kunshan, with diverse strains and amino acid variations potentially affecting vaccination efficacy and FCV detection. Notably, analysis pinpointed certain strains’ association with FCV-virulent systemic disease pathotypes. This investigation sheds light on FCV dynamics, which may aid in developing better prevention strategies and future vaccine designs against circulating FCV genotypes.
Challenges and barriers of using large language models (LLM) such as ChatGPT for diagnostic medicine with a focus on digital pathology – a recent scoping review
Authors: Ullah Ehsan , Parwani Anil , Baig Mirza Mansoor , Singh Rajendra
Published: February 2024

Background

The integration of large language models (LLMs) like ChatGPT in diagnostic medicine, with a focus on digital pathology, has garnered significant attention. However, understanding the challenges and barriers associated with the use of LLMs in this context is crucial for their successful implementation.

Methods

A scoping review was conducted to explore the challenges and barriers of using LLMs, in diagnostic medicine with a focus on digital pathology. A comprehensive search was conducted using electronic databases, including PubMed and Google Scholar, for relevant articles published within the past four years. The selected articles were critically analyzed to identify and summarize the challenges and barriers reported in the literature.

Results

The scoping review identified several challenges and barriers associated with the use of LLMs in diagnostic medicine. These included limitations in contextual understanding and interpretability, biases in training data, ethical considerations, impact on healthcare professionals, and regulatory concerns. Contextual understanding and interpretability challenges arise due to the lack of true understanding of medical concepts and lack of these models being explicitly trained on medical records selected by trained professionals, and the black-box nature of LLMs. Biases in training data pose a risk of perpetuating disparities and inaccuracies in diagnoses. Ethical considerations include patient privacy, data security, and responsible AI use. The integration of LLMs may impact healthcare professionals’ autonomy and decision-making abilities. Regulatory concerns surround the need for guidelines and frameworks to ensure safe and ethical implementation.

Conclusion

The scoping review highlights the challenges and barriers of using LLMs in diagnostic medicine with a focus on digital pathology. Understanding these challenges is essential for addressing the limitations and developing strategies to overcome barriers. It is critical for health professionals to be involved in the selection of data and fine tuning of the models. Further research, validation, and collaboration between AI developers, healthcare professionals, and regulatory bodies are necessary to ensure the responsible and effective integration of LLMs in diagnostic medicine.