bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncovering the gray zone: mapping the global landscape of direct-to-consumer businesses offering interventions based on secretomes, extracellular vesicles, and exosomes
Authors: Asadpour Atiyeh , Yahaya Badrul Hisham , Bicknell Katrina , Cottrell Graeme S. , Widera Darius 
Published: May 2023

Abstract
Background
The last decade has seen a significant increase in media attention, industrial growth, and patient interest in stem cell-based interventions. This led to a rise in direct-to-consumer businesses offering stem cell “therapies” for multiple indications with little evidence of safety and efficacy. In parallel, the use of stem cell secretomes as a substitute for stem cell transplantation has become an increasing trend in regenerative medicine with multiple clinical trials currently assessing their efficacy and safety profile. As a result, multiple businesses and private clinics have now started to exploit this situation and are offering secretome-based interventions despite the lack of supporting data. This poses significant risks for the patients and could lead to a credibility crisis in the field.

Methods
Internet searches were used to locate clinics marketing and selling interventions based on stem cell secretomes, exosomes, or extracellular vesicles. Data were extracted from websites with a particular focus on the global distribution of the businesses, the cellular source of the secretome, the indication spectrum, and the pricing of the provided services. Lastly, the types of evidence used on the websites of the businesses to market their services were extracted.

Results
Overall, 114 companies market secretome-based therapies in 28 countries. The vast majority of the interventions are based on allogenic stem cells from undisclosed cellular sources and skin care is the most marketed indication. The price range is USD99–20,000 depending on the indication.

Conclusions
The direct-to-consumer industry for secretome-based therapies appears to be primed for growth in the absence of appropriate regulatory frameworks and guidelines. We conclude that such business activity requires tight regulations and monitoring by the respective national regulatory bodies to prevent patients from being conned and more importantly from being put at risk.
Existence of positive periodic solutions for a periodic predator–prey model with fear effect and general functional responses
Authors: Guo Ke , Ma Wanbiao 
Published: May 2023

AbstractThis paper investigates the existence of positive periodic solutions for a periodic predator-prey model with fear effect and general functional responses. The general functional responses can cover the Holling types II and III functional response, the Beddington–DeAngelis functional response, the Crowley–Martin functional response, the ratio-dependent type with Michaelis–Menten type functional response, etc. Some new sufficient conditions for the existence of positive periodic solutions of the model are obtained by employing the continuation theorem of coincidence degree theory and some ingenious estimation techniques for the upper and lower bounds of the a priori solutions of the corresponding operator equation. Our results considerably improve and extend some known results.
Validation of the first computerized indicator for orthopaedic surgical site infections in France: ISO-ORTHO
Authors: Grammatico-Guillon Leslie , Banaei-Bouchareb Linda , Solomiac Agnès , Miliani Katiuska , Astagneau Pascal , May-Michelangeli Laetitia 
Published: May 2023

Abstract
Background
The French national authority for health (HAS) develops in-hospital indicators for improving quality of care, safety and patient outcome. Since 2017, it has developed a measurement of surgical site infections (SSI) after total hip or knee arthroplasty (TH/KA) by using a computerized indicator, called ISO-ORTHO, based on a hospital discharge database (HDD) algorithm. The aim of the study was to assess the performance of this new indicator .

Methods
The ISO-ORTHO performance was estimated via its positive predictive value (PPV) among adult patients having undergone a TH/KA between January 1st and September 30th 2018, based on the orthopaedic procedure codes. Patients at very high risk of SSI and/or with SSI not related to the in-hospital care were excluded. SSI were detected from the date of admission up to 90 days after the TH/KA using the ISO-ORTHO algorithm, based on 15 combinations of ICD-10 and procedure codes. Its PPV was estimated by a chart review in volunteer healthcare organisations (HCO).

Results
Over the study period, 777 HCO including 143,227 TH/KA stays were selected, providing 1,279 SSI according to the ISO-ORTHO indicator. The 90-day SSI rate was 0.89 per 100 TH/KA stays (0.98% for THA and 0.80% for TKA). Among the 448 HCO with at least 1 SSI, 250 HCO participated in reviewing 725 SSI charts; 665 were confirmed, giving a PPV of 90.3% [88.2-92.5%], 89.9% [87.1-92.8%] in THA and 90.9% [87.7-94.2%] in TKA.

Conclusions
The PPV of ISO-ORTHO over 90% confirms its validity for any use according to the HAS method. ISO-ORTHO and detailed information were provided in 2020 to HCO and used for quality assessment and in-hospital risk management.
Coordinated response of milk bacterial and metabolic profiles to subacute ruminal acidosis in lactating dairy cows
Authors: Mu Yingyu , Qi Wangpan , Zhang Tao , Zhang Jiyou , Mao Shengyong 
Published: May 2023

Abstract
Background
Bovine milk is an important source of nutrition for human consumption, and its quality is closely associated with the microbiota and metabolites in it. But there is limited knowledge about the milk microbiome and metabolome in cows with subacute ruminal acidosis.

Methods
Eight ruminally cannulated Holstein cows in mid lactation were selected for a 3-week experiment. The cows were randomly allocated into 2 groups, fed either a conventional diet (CON; 40% concentrate; dry matter basis) or a high-concentrate diet (HC; 60% concentrate; dry matter basis).

Results
The results showed that there was a decreased milk fat percentage in the HC group compared to the CON group. The amplicon sequencing results indicated that the alpha diversity indices were not affected by the HC feeding. At the phylum level, the milk bacteria were dominated by Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes both in the CON and HC groups. At the genus level, the HC cows displayed an improved proportion of Labrys (P = 0.015) compared with the CON cows. Results of both the principal components analysis and partial least squares of discriminant analysis of milk metabolome revealed that samples of the CON and HC groups clustered separately. A total of 31 differential metabolites were identified between the two groups. Of these, the levels of 11 metabolites decreased (α-linolenic acid, prostaglandin E2, L-lactic acid, L-malic acid, 3-hydroxysebacic acid, succinyladenosine, guanosine, pyridoxal, L-glutamic acid, hippuric acid, and trigonelline), whereas the levels of the other 20 metabolites increased in the HC group with respect to the CON group (P < 0.05).

Conclusion
These results suggested that subacute ruminal acidosis less impacted the diversity and composition of milk microbiota, but altered the milk metabolic profiles, which led to the decline of the milk quality.
Effects of tannic acid on the immunity and intestinal health of broiler chickens with necrotic enteritis infection
Authors: Xu Huiping , Fu Jianyang , Luo Yimeng , Li Peng , Song Bochen , Lv Zengpeng , Guo Yuming 
Published: May 2023

Abstract
Background
In broiler chickens, necrotic enteritis (NE) infection can reduce production performance. Tannic acid has shown great potential as a treatment of NE in broilers. However, the appropriate dosage of tannic acid in NE of broilers and the improvement effect on intestinal health are not very clear. In this study, we aimed to investigate the effects of different doses of tannic acid on the production performance, immunity, and intestinal health of broilers by constructing an NE model with C. perfringens infection and determining the appropriate dosage of tannic acid with regard to NE.

Results
Challenged birds showed significant reduction in body weight, villus height, and the ratio of villus height to crypt depth (P < 0.05) and increase in the feed consumption gain ratio, intestinal lesion score, and crypt depth (P < 0.05). The infection significantly reduced the relative Bacteroidota and Ligilactobacillus abundance (P < 0.05) and increased the ratio of Firmicutes/Bacteroidota and cecal content of C. perfringens (P < 0.05). Challenged birds fed diets supplemented with tannic acid showed significantly increased mRNA expression of nutrient transport carriers and intestinal barrier genes and growth performance and reduced serum zonulin and endotoxin levels (P < 0.05). Addition of tannic acid to the diet inhibited the inflammatory response by reducing the number of coccidia oocysts in feces and the content of C. perfringens in the cecum. Specifically, tannic acid reduced the serum levels of C reactive protein, myeloperoxidase, and specific IgY and ileal mucosal secretory immunoglobulin A levels in the ileal mucosa compared with those in the NE-infected birds. NE-infected birds fed diets supplemented with tannic acid also showed significantly increased relative Anaerocolumna, Thermoanaerobacterium, and Thermosinus abundance (P < 0.05); their microbial composition and functional predictions were similar to those of the NC group.

Conclusions
Tannic acid in the diet alleviated NE by enhancing the intestinal barrier and absorption function. The recommended dietary tannic acid additive level is 500–750 mg/kg. Our study findings would be useful in reducing related economic losses in the broiler industry.
Validation of the Osaka basin velocity model by waveform simulation using sources inverted with reciprocal Green’s functions
Authors: Petukhin Anatoly , Iwasaki Yoshinori 
Published: May 2023

AbstractTo advance the methodology for validating velocity models by waveform comparison, we estimated source parameters for small magnitude earthquakes that can be approximated by point sources. Instead of using published source models, we used the reciprocity method to calculate 3D Green’s functions using the target velocity structure itself, and then inverted the earthquake sources. This method greatly reduces the calculations required compared to a full inversion of the source mechanism, depth, and source duration (risetime), making it possible to reproduce input ground motions in the target basin. Here, we validated the Japan Integrated Velocity Structure model of the Osaka basin using five earthquakes around the Osaka basin; these earthquakes allowed us to investigate the impact of the incident waves’ propagation directions. We first estimated source parameters using records at control bedrock sites surrounding the Osaka basin to reproduce the input ground motions. Then, we conducted a 3D finite-difference simulation for sites within the basin. By mapping the distributions of misfit values for individual waveforms, peak ground velocities, and response spectra, we were able to identify areas in the basin that require additional tuning of the velocity model.
Graphical Abstract
A simple method to evaluate the uncertainty of magnetotelluric forward modeling for practical three-dimensional conductivity structure models
Authors: Baba Kiyoshi 
Published: May 2023

AbstractThe forward calculation of magnetotelluric (MT) responses is generally assumed to be sufficiently accurate compared with typical observational errors in practical modeling and inversion studies. Although the uncertainty of the forward calculation may be examined by comparison with analytical or other numerical solutions for some simple models, such an examination does not guarantee that the uncertainty is similar for more realistic complex structures. In this study, I propose a simple method to evaluate the uncertainty of MT forward modeling for practical three-dimensional (3D) conductivity structure models in a Cartesian coordinate system. The method is based on the idea that the horizontal coordinate system can be selected arbitrarily for a general 3D structure. The synthesized MT responses are ideally identical irrespective of the selection but are different because of the difference in discretization angles, boundary values, and numerical errors. By synthesizing MT responses to the model in several different coordinate systems, the mean, standard deviation, and coefficient of variation can be calculated. These statistics provide quantitative information on how stably the forward calculations synthesize MT responses under the given conditions of the structure model, observation array, periods, numerical algorithm for the forward modeling, and mesh design. The proposed method was applied to two practical situations of seafloor MT arrays in the northwestern Pacific and southern Atlantic and a land MT array in Hokkaido, Japan. The results show that the uncertainty is comparable to real observation errors and is significantly dependent on the MT impedance element, period, site, structure model, and horizontal coordinate system. The uncertainty of the forward calculation should be considered for each element, period, and site to quantitatively evaluate how well a given model explains the data. I propose a new root-mean-square in which the residuals are normalized by both the standard errors of the MT responses observed and synthesized. This would help avoid overfitting data in the inversion analysis by ignoring the uncertainty of the forward calculation. This method is also useful for testing the appropriate selection of the coordinate system and mesh design.
Graphical Abstract
Formative evaluation prior to implementation of a brief treatment for posttraumatic stress disorder in primary care
Authors: Valentine Sarah E. , Fuchs Cara , Olesinski Elyse A. , Sarkisova Natalya , Godfrey Laura B. , Elwy A. Rani 
Published: May 2023

Abstract
Background
Successful implementation of evidence-based treatments (EBT) for posttraumatic stress disorder (PTSD) in primary care may address treatment access and quality gaps by providing care in novel and less stigmatized settings. Yet, PTSD treatments are largely unavailable in safety net primary care. We aimed to collect clinician stakeholder data on organizational, attitudinal, and contextual factors relevant to EBT implementation.

Methods
Our developmental formative evaluation was guided by the Consolidated Framework for Implementation Research (CFIR), including (a) surveys assessing implementation climate and attitudes towards EBTs and behavioral health integration and (b) semi-structured interviews to identify barriers and facilitators to implementation and need for augmentation. Participants were hospital employees (N = 22), including primary care physicians (n = 6), integrated behavioral health clinicians (n = 8), community wellness advocates (n = 3), and clinic leadership (n = 5). We report frequency and descriptives of survey data and findings from directed content analysis of interviews. We used a concurrent mixed-methods approach, integrating survey and interview data collected simultaneously using a joint display approach. A primary care community advisory board (CAB) helped to refine interview guides and interpret findings.

Results
Stakeholders described implementation determinants of the EBT related to the CFIR domains of intervention characteristics (relative advantage, adaptability), outer setting (patient needs and resources), inner setting (networks and communication, relative priority, leadership engagement, available resources), and individuals involved (knowledge and beliefs, cultural considerations). Stakeholders described strong attitudinal support (relative advantage), yet therapist time and capacity restraints are major PTSD treatment implementation barriers (available resources). Changes in hospital management were perceived as potentially allowing for greater access to behavioral health services, including EBTs. Patient engagement barriers such as stigma, mistrust, and care preferences were also noted (patient needs and resources). Recommendations included tailoring the intervention to meet existing workflows (adaptability), system alignment efforts focused on improving detection, referral, and care coordination processes (networks and communication), protecting clinician time for training and consultation (leadership engagement), and embedding a researcher in the practice (available resources).

Conclusions
Our evaluation identified key CFIR determinants of implementation of PTSD treatments in safety net integrated primary care settings. Our project also demonstrates that successful implementation necessitates strong stakeholder engagement.
Protocol for the production of micro- and nanoplastic test materials
Authors: Parker Luke A. , Höppener Elena M. , van Amelrooij Edward F. , Henke Sieger , Kooter Ingeborg M. , Grigoriadi Kalouda , Nooijens Merel G. A. , Brunner Andrea M. , Boersma Arjen 
Published: May 2023

AbstractMicro- and nanoplastics (MNP) are ubiquitous, but little is known about the risks they pose to human health. Currently available data are of limited use for developing relevant risk assessments due to poor quality control, the lack of a standardised approach to particle characterisation and environmental analysis, and the use of test materials that do not reflect those found in the environment. A set of well-characterised MNP test materials would greatly alleviate this. Here, we present a robust method to produce, fractionate and characterise such test materials of PP and PVC. Initial size reduction of commercial powders or pellets to 500 µm was performed using a centrifugal mill under cryogenic conditions. Further ball-milling between room temperature and -50 °C in 1-propanol was then performed to reach the final particle sizes. Fractionation into size ranges of < 1, 1–5, 5–10, 10–30, 90–180 and 180–300 µm was performed by sedimentation and filtration. Characterisation of the reference materials through SLS, SEM–EDX, XRF and TGA demonstrated that the fractions were of the desired size and levels of contamination from the procedure were < 1 wt%. Stability testing in both 1-propanol and 0.05 wt% BSA solution showed that whilst some agglomeration occurred during storage in 1-propanol the suspensions were stable in BSA over 9 months and some of the previous agglomeration was reversed.
Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development
Authors: Tsilingiris Dimitrios , Schimpfle Lukas , von Rauchhaupt Ekaterina , Sulaj Alba , Seebauer Lukas , Bartl Hannelore , Herzig Stephan , Szendroedi Julia , Kopf Stefan , Kender Zoltan 
Published: May 2023

Abstract

Aim
To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development.

Methods
A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as “healthy” and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence.

Results
Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P &lt; .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P &lt; .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, “sensory loss” was most strongly associated with PN development (adjusted HR, 4.35; P = .011).

Conclusion
We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.
Fractional spinal anesthesia and systemic hemodynamics in frail elderly hip fracture patients
Authors: Olsen Fredrik , Hård af Segerstad Mathias , Dalla Keti , Ricksten Sven-Erik , Nellgård Bengt 
Published: May 2023

Background: Systemic haemodynamic effects of intrathecal anaesthesia in an aging and frail population has not been well investigated. We examined the systemic haemodynamics of fractional spinal anaesthesia following intermittent microdosing of a local anaesthetic and an opioid. Methods: We included 15 patients aged over 65 with significant comorbidities, planned for hip fracture repair. Patients received a spinal catheter and cardiac output monitoring using the LiDCOplus system. All measurements were performed prior to start of surgery. Invasive mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance index (SVRI), heart rate and stroke volume index (SVI) were registered. Two doses of bupivacaine 2.25 mg and fentanyl 15 µg were administered with 25-minute intervals. Hypotension was defined as a fall in MAP by >30% or a MAP <65 mmHg. Results: The incidence of hypotension was 30%. Hypotensive patients (n=5) were treated with low doses of norepinephrine (0.01-0.12 µg/kg/min). MAP showed a maximum reduction of 17% at 10 minutes following the first dose. CI, systemic vascular resistance index and stroke volume index decreased by 10%, 6%, and 7%, respectively, while heart rate was unchanged over time. After the second dose, none of the systemic haemodynamic variables were affected. Conclusions: Fractional spinal anaesthesia administered prior to surgery induced a minor to moderate fall in MAP, mainly caused by a reduction in cardiac output, induced by systemic venodilation, causing a fall in venous return. Our results are contrary to the widely held belief that hypotension is mainly the result of a reduction of systemic vascular resistance.