bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of an App for Promoting Advance Care Planning and Motivating Patients to Write their Advance Directives
Authors: Schöpfer Céline , Bollondi Catherine , Moussa Mohamed Amir , Sommer Johanna , Clavien Christine
Published: January 2023

Background
We developed Accordons-nous, a smartphone app to support patients in the advance care planning (ACP) process. The app raises awareness and facilitates communication on this sensitive topic. It helps patients to express their values and preferences for care, and to write their advance directives (AD).
Objective
Measure the impact of distributing Accordons-nous, compared to the distribution of a leaflet, on common patients’ propensity to engage in an ACP process. Secondary objectives are to test the effect of socio-demographic factors (age, health state, gender, study level) on the propensity to engage in ACP.
Methods
Pre-post randomized control study. Participants were common patients approached in medical waiting rooms. They received the app (treatment) or an information leaflet (control) and responded to two questionnaires: one at recruitment and a second 2–4 weeks later. We measured improvement on four variables relevant to ACP: reported Contemplation of an event relevant to ACP, Decision about treatment in case of that event, Discussion about it with relatives or health care professionals, and Writing advance directives. Statistical analysis included between groups comparisons of pre-post differences with 2-sample tests for equality of proportions and logistic regression models.
Results
We recruited 473 participants and obtained full responses from 312. Overall the intervention (control and treatment together) affected positively the mean reported ACP engagement on all variables: new or renewed Contemplation 54%; increase in Decision + 8%, Discussion + 11%, and Writing + 1%, compared to the baseline. Compared to the control (leaflet), the treatment group (app) had a larger effect size on all variables: between groups difference in Contemplation + 11% (logistic regression, p = .05), Decision + 1% (but p = .94 on this variable), Discussion + 5% (p = .05), and Writing AD + 5% (p = 0.03). Moreover, increase in age is positively correlated with having written AD at inclusion (21% among retired compared to 2% among young adults) and with the propensity to write AD after our intervention (logistic regression, p = .001). Other factors tested (frequency of consultations, gender, level of education) had no effect on participants’ ACP engagement.
Conclusions
When distributed without specific counselling, our tool is efficient to increase reported ACP engagement although the effect sizes remain modest. Further studies are needed to investigate whether the app could profit more to ACP engagement when it is used by professionals in dedicated ACP consultations.
Methodological Quality of Retrospective Observational Studies Investigating Effects of Diabetes Monitoring Systems: a Systematic Review
Authors: Jiu Li , Wang Junfeng , Kamusheva Maria , Dimitrova Maria , Tachkov Konstantin , Milushewa Petya , Mitkova Zornitsa , Petrova Guenka , Vreman Rick , Mantel-Teeuwisse Aukje K. , Goettsch Wim
Published: January 2023

Background
Retrospective observational studies (ROSs) have been frequently used to investigate treatment effects of diabetes monitoring systems (DMS), i.e. medical devices to monitor blood glucose. However, due to quality concerns, the findings of such studies were often questioned by clinical, regulatory, or health technology assessment decision-makers. We aimed to conduct a systematic review to assess the methodological quality of ROSs investigating DMS effects, and to explore the trend in quality change over time.
Methods
Embase, PubMed, Web of Science, and Scopus were systematically searched for English-language articles published from January 2012 to March 2021. Randomized controlled trials or other prospective studies were manually excluded. The ROBINS-I (Risk Of Bias In Non-randomized Studies – of Interventions) was used for assessing RoB. To investigate the quality change over time, we divided the study into three subgroups according to publication year, and compared the proportion of studies with the same quality level among the three subgroups.
Results
We identified 4926 articles, of which 72 were eligible for inclusion. Twenty-six studies were published before 2018, 22 in 2018 or 2019, and 24 after 2019. The overall methodological quality was quite low, as 61 (85%) studies were graded as facing critical or serious RoB. Also, the overall methodological quality did not substantially improve over time. The major contributors to low quality included confounding, missing data, and selection of the reported results.
Conclusions
The retrospective observational studies investigating DMS effects generally had a high risk of bias, and this did not substantially improve in the past ten years. Thus, clinical, regulatory, or HTA decision-makers may need strategies to effectively exploit these suboptimal studies. Also, to further improve study quality, extra efforts may be needed, such as guiding the tool selection regarding quality improvement in the tools.
The value of allied health professional research engagement on healthcare performance: a systematic review
Authors: Chalmers Sophie , Hill James , Connell Louise , Ackerley Suzanne J , Kulkarni Amit A , Roddam Hazel
Published: January 2023

Background

Existing evidence suggests that clinician and organisation engagement in research can improve healthcare performance. However, current evidence has considered the relationship across all healthcare professions collectively. With the increase in allied health professional (AHP) clinical academic and research activity, it is imperative for healthcare organisations, leaders and managers to understand research engagement within these specific clinical fields. This systematic review aims to examine the value of research engagement by allied health professionals and organisations on healthcare performance.

Methods

This systematic review had a two-stage search strategy. Firstly, the papers from a previous systematic review examining the effect of research engagement in healthcare were screened to identify relevant papers published pre-2012. Secondly, a multi-database search was used to update the previous review but with a specific focus on allied health to identify publications from 2012 to date. Studies which explored the value of allied health research engagement on healthcare performance were included. All stages of the review were conducted by two reviewers independently, plus documented discussions with the wider research team when discrepancies occurred. Each study was assessed using the appropriate critical appraisal tool developed by the Joanna Briggs Institute.

Results

Twenty-two studies were included, of which six were ranked as high importance. This sample comprised mixed research designs. Overall, the findings indicated positive improvements in processes of care. The review also identified the most common mechanisms which may link research engagement with improvements to processes of care.

Conclusion

This landmark review is the first benchmark of evidence that explicitly shows improved processes of care and outcomes from AHP research engagement. The lack of transparent reporting of AHP research engagement highlights the need for clear recommendations in the design of future prospective studies. These proposals specifically include greater transparency in relation to AHP involvement, mechanisms and types of research engagement. The inclusion of these aspects as an integral component of future intervention study designs may contribute essential evidence of the value and impact of AHP research engagement.
Trial registration: This systematic review protocol was registered with the international prospective register of systematic reviews, PROSPERO (registration number CRD42021253461).
Assessment of the role of neutrophil-lymphocyte ratio as a prognostic biomarker in breast cancer patients: a cross-sectional study
Authors: Takada Koji , Kashiwagi Shinichiro , Iimori Nozomi , Kouhashi Rika , Yabumoto Akimichi , Goto Wataru , Asano Yuka , Tauchi Yukie , Ogisawa Kana , Morisaki Tamami , Shibutani Masatsune , Tanaka Hiroaki , Maeda Kiyoshi
Published: January 2023

Background
Peripheral blood neutrophil–lymphocyte ratio (NLR) has been reported to predict the effects of surgery and chemotherapy in breast cancer patients. However, majority of the studies performed only one-time evaluation before commencement of treatment, while few evaluated the ratio over a period of time. In this study, we calculated NLR before surgery and postoperative adjuvant chemotherapy for patients with resectable breast cancer who underwent surgery as the initial treatment, and examined its correlation with clinicopathological factors and prognosis.
Methods
A total of 1095 patients with primary resectable breast cancer underwent curative resection as the first line of treatment between December 2007 and October 2018. Of these 1095 patients, 178 were included in this study. Peripheral blood was collected before, and after the surgery. Preoperative NLR was evaluated during the first hospital visit before biopsy. Postoperative NLR was evaluated using peripheral blood collected immediately prior to postoperative adjuvant chemotherapy. The cut-off values of NLR were set to 3, which has been reported to be the most commonly used value.
Results
Examination of postoperative NLR and prognosis in 24 breast cancer patients with higher pre-NLR revealed no significant difference (disease-free survival [DFS], p = 0.320; overall survival [OS], p = 0.409, log-rank test). However, when post-NLR and prognosis were examined in 154 breast cancer patients with lower pre-NLR, the lower post-NLR group showed significant prolongation in DFS (p < 0.001, log-rank test). Furthermore, OS tended to be prolonged in the lower post-NLR group (p = 0.056, log-rank test). Multivariate analysis of DFS in 154 breast cancer patients with lower pre-NLR showed that large tumors (hazard ratio [HR]: 4.132, p = 0.009), nuclear grade 3 (HR: 2.746, p = 0.043), and higher post-NLR (HR: 4.639, p = 0.003) were independent factors.
Conclusions
This study suggests that prognosis of breast cancer patients can be predicted by evaluating the NLR over time.
Impact of treated vs. un-treated municipal wastewater irrigations in Eggplant (Solanum melongena L.) on soil-plant metal translocation, crop yield and consumer health hazard
Authors: Ramesh Thorun Patel Kolar , Lal Khajanchi , Kaur Ravinder , Gopi Rosin Kunnamuzhath , Kumar Sarvendra , Suman Archna , Rathore Sanjay Singh
Published: January 2023

The present study assessed the impacts of municipal wastewater treated through a constructed wetland on the crop yield of eggplant and human health hazards, due to the consumption of the metal and pathogen enriched eggplant fruit. The impacts were compared with groundwater the untreated municipal wastewater irrigations, applied individually and conjunctively. The soil irrigated with untreated wastewater had 1.94, 2.41, 4.68 and 3.29 times higher soil organic carbon, nitrogen, phosphorus, potassium and 2.18–4.46 times higher soil micronutrient contents, respectively compared to soil irrigated with treated wastewater. The plant nutrient uptake and crop yields from the untreated wastewater irrigated plots were 22–23 and 10–18% higher than those from the groundwater; treated wastewater and conjunctively irrigated plots. Compared to the untreated wastewater irrigated plots, the plots receiving treated wastewaters (having 14 to 86% lower metal concentrations) or conjunctive water use had 47 to 50% reduced trace metal built-ups and 31–50% and 14–31% reduced consumer health hazards, respectively. Further, the produce generated from treated wastewater had 36% lower total heterotrophic bacteria and 70% lower total coli-form. The produce obtained from the conjunctively irrigated plots also had 24% lower total heterotrophic bacteria and 46% lower total coli-forms but these values were still 20 and 76% higher than those from the treated wastewater irrigated plots thereby confirming safer reuse potential of the treated wastewaters compared to either the conjunctive use or the direct disposal of untreated wastewaters in the vegetable production systems.
Simulated microgravity effects impair macrophage phagocytosis by regulating cytoskeleton-associated proteins
Authors: Yang Hui , Shi Guolin , Wang Sufang , Zhao Wenjuan , Zhang Nu
Published: January 2023

Many studies have shown that microgravity can cause damage to the immune system of astronauts, posing serious health risks to astronauts in space flight. In particular, macrophages, as an important target for studying the effects of microgravity on immunity, its regulation mechanism by microgravity is still unclear. In this study, Random Positioning Machines (RPM) and Rotary Cell Culture System (RCCS) were employed for understanding the effect of simulated microgravity (SMG) effects on the immune function of macrophages in 48 h. Firstly, under simulated microgravity conditions, the cells atrophied, the pseudopodia on the surface were reduced, and the phagocytosis and proliferation of macrophages were significantly dropped. Secondly, SMG attenuated the immune response of macrophages by reducing the expression of phagocytosis-related receptors on the surface of macrophages, which may be the main reason for the phagocytosis decline. Finally, by transcriptome analysis and molecular biology validation, the results suggest that SMG also leads to a decreased expression of cytoskeleton-related proteins, which may be indicate an alternative mechanism for SMG affecting the immune response of macrophages. Our findings can provide guidance on immune damage caused by microgravity and help protect the health of astronauts.
Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity
Authors: Dam Koos van , Volkers Adriaan , Wieske Luuk , Stalman Eileen , Kummer Laura , kempen Zoe van , Killestein Joep , Tas Sander , Boekel Laura , Wolbink Gertjan , Kooi Anneke van der , Raaphorst Joost , Takkenberg Bart , D'Haens Geert , Spuls Phyllis , Bekkenk Marcel , Musters Annelie , Post Nicoline , Bosma Angela , Hilhorst Marc , Vegting Yosta , Bemelman Frederike , Voskuyl Alexandre , Broens Bo , Sanchez Agner Parra , Els Cecile van , de Wit Jelle , Rutgers Abraham , de Leeuw Karina , Horvath Barbara , Verschuuren Jan , Ruiter Annabel , Ouwerkerk Lotte van , Woude Diane van der , Allaart Renee , Teng Onno , Paassen Pieter van , Busch Matthias , Jallah Papay , Brusse Esther , Doorn Pieter van , Baars Adaja , Hijnen DirkJan , Schreurs Corine , Pol Ludo van der , Goedee Stephan , Steenhuis Maurice , Keijzer Sofie , Keijser Jim , Cristianawati Olvi , Brinke Anja ten , Verstegen Niels , Ham Marieke van , Rispens Theo , Kuijpers Taco , Lowenberg Mark , Eftimov Filip
Published: January 2023

Background: Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs.
Methods: IMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies.
Results: In total, 193 IMID patients on ISP and 113 controls were included. Serum samples from 185 participants were available, with a median time of 173 days between infection and sample collection. The rate of seropositive IMID patients on ISPs was 78% compared to 100% in controls (p<0.001). Seropositivity rates were lowest in patients on anti-CD20 (40.0%) and anti-tumor necrosis factor (TNF) agents (60.5%), as compared to other ISPs (p<0.001 and p<0.001, respectively). Increased disease activity after infection was reported by 68 of 260 patients (26.2%; 95% CI 21.2–31.8%), leading to ISP intensification in 6 out of these 68 patients (8.8%).
Conclusion: IMID patients using ISPs showed reduced long-term humoral immune responses after primary SARS-CoV-2 infection, which was mainly attributed to treatment with anti-CD20 and anti-TNF agents. Increased disease activity after SARS-CoV-2 infection was reported commonly, but was mostly mild.
Trial registration
NL74974.018.20, Trial ID: NL8900. Registered on 9 September 2020.
Rule Rationality Leads to Tangential Bifurcation and Phase Transition in Dynamic Production
Authors: Zhao Guo
Published: January 2023

The classical theory of production is based on the unrealistic assumption of perfect rationality, under which firms maximize profits in all situations. In contrast, under conditions of risk and bounded rationality, firms may make decisions based on behavioral rule of thumb. However, we have little insight into how a firm’s decision resulting from rule rationality affects the process of economic growth and industrial upgrading. Here we extend profit maximization by integrating production theory with rule rationality, proposing a behavioral model of dynamic production under the joint constraints of technology, budget and no arbitrage. Theoretical analysis shows that rule rationality may lead to a tangential bifurcation from the profit maximization point, across which the economy may bifurcate into a stable capital-intensive equilibrium and an unstable labor-intensive equilibrium. Further, numerical simulation shows that rule rationality may result in a phase transition from labor-intensive equilibrium into capital-intensive equilibrium as the capital/labor ratio reaches certain threshold level. These findings are consistent with the empirical pattern of club convergence and industrial mutation.
Diet-habitat ecology of invasive tilapia and native fish in a tropical river catchment following a tilapia invasion
Authors: O'Mara Kaitlyn , Venarsky Michael , Marshall Jonathan , Stewart-Koster Ben
Published: January 2023

Many species of tilapia (a collection of fish species from the cichlidae family) have biological traits that make them successful invaders. While widespread herbivory has been observed in many tilapia species, knowledge on habitat preferences and tilapia interactions with native fish food webs is limited. This study used stomach contents and stable isotope analysis of spotted tilapia (Pelmatolapia mariae) and Mozambique tilapia (Oreochromis mossambicus), and stable isotopes of common native fish species to explore relationships between habitat and diet for fish food webs in the Mitchell River, northern Australia, three years after tilapia were detected in the catchment. While plant material was the most abundant item in tilapia stomachs, some also contained other items in small quantities, such as fish eggs, small shrimp, and bivalves. Macrohabitat type (in-channel (no tilapia), off-channel (no tilapia), weir (tilapia present)) was related to native fish food web structure, with weir food webs showing similarities to off-channel food webs. In-channel food webs were more constrained than weir or off-channel food webs, reflecting a more limited range of available food sources. Off-channel habitats including creeks and wetlands were most similar to weir habitats and may therefore be most at risk of colonization as tilapia spread throughout the catchment. This study clearly demonstrated that the successful rapid invasion of these two tilapia species is linked to suitable habitat with abundant food that fuels growth and reproduction. These findings increase understanding of diet related habitat use during new tilapia invasions and trophic interactions with native species.
Comparative study of molecular and non-molecular tools for peste des petits ruminants virus detection in West African Dwarf goats
Authors: Muritala Ismaila , Bemji Martha N. , Ozoje Michael O. , Ajayi Olusola L. , Oluwayinka Eniope B. , Sonibare Adekayode O. , James Ikechukwu J. , Ibeagha-Awemu Eveline M.
Published: January 2023

Peste des petits ruminants (PPR) causes severe economic losses to many countries of the world where the disease is endemic. It has been targeted for global eradication by 2030 following the successful eradication of rinderpest in 2011. The proposed eradication program would benefit from efficient and relatively reliable diagnostic tools for early PPR virus (PPRV) detection. A total of 33 eight to 12 months old West African Dwarf (WAD) goats were used. Nineteen goats infected by comingling with two PPR virus positive animals formed the infected group (PPRV-infected goats) while 14 non-infected goats formed the control group (CTG). The suitability of a molecular method (Hydroxyl naphthol blue (HNB) staining of reverse transcription loop mediated isothermal amplification (RT-LAMP)) and a non-molecular tool (haemagluttination assay (HA)) were compared for their sensitivity to detect the PPRV in PPRV-infected goats and non-infected CTG. PPR disease severity in WAD goats at different days post infection (dpi) was evaluated by clinical scoring and haemagluttination titre (HAT). HNB staining RT-LAMP reaction and HA showed sensitivities of 100% and 73.68%, respectively, for PPRV detection. Expression of PPR clinical signs began from 3 dpi, attained peak at 5 dpi, thereafter showed irregular patterns till 24 dpi. Evaluation of HAT in PPRV-infected goats at 12 dpi ranged from 2 to 64 haemagluttination units (HAU), while CTG goats had 0 HAU. In conclusion, HNB staining RT-LAMP assay demonstrated reasonable potential for accurate diagnoses of PPRV and as an important diagnostic tool in areas with poor electricity supply and less sophisticated laboratory equipment.
Efficacy of erector spinae plane block versus thoracic paravertebral block for postoperative analgesia in modified radical mastectomy: a randomized controlled trial
Authors: Santonastaso Domenico Pietro , Chiara Annabella , Righetti Roberto , Marandola Diego , Sica Andrea , Bagaphou Claude T. , Rosato Chiara , Tognù Andrea , Curcio Annalisa , Lucchi Leonardo , Russo Emanuele , Agnoletti Vanni
Published: January 2023

Background
Postoperative analgesia in breast surgery is difficult due to the extensive nature of the surgery and the complex innervation of the breast; general anesthesia can be associated with regional anesthesia techniques to control intra- and post-postoperative pain.
This randomized controlled study aimed to compare the efficacy of the erector spinae plane block and the thoracic paravertebral block in radical mastectomy procedures with or without axillary emptying.
Methods
This prospective, randomized controlled trial included 82 adult females who were randomly divided into two groups using a computer-generated random number. Both groups received general anesthesia, Groups P and E (41 patients each) associated with a single-shot thoracic paravertebral block and a single-shot erector spinae plane block, respectively.
Postoperative pain intensity (expressed as Numeric Rating Scale), patients who needed rescue analgesic, intra- and post-operative opioid consumption, post-operative nausea and vomiting, length of stay, adverse events, chronic pain at 6 months, andthe patient’s satisfaction were recorded.
Results
At 2 h (p<0.001) and 6 h (p=0.012) the Numeric Rating Scale was significantly lower in Group P.
The Numeric Rating Scale at 12, 24, and 36 postoperative hours did not show significant differences.
There were no significant differences also in the number of patients requiring rescue doses of NSAIDs, in intra- and post-operative opioid consumption, in post-operative nausea and vomiting episodes and in the length of stay.
No failures or complications occurred in the execution of techniques and none of the patients reported any chronic pain at six months from the surgery.
Conclusions: Both thoracic paravertebral block and erector spinae plane block can be effectively used in controlling post-mastectomy pain and reduce intra- and post-operative opioid consumption.
Trial registration
The study was prospectively registered on Clinicaltrials.com (trial identifier NCT04457115) (first registration 27/04/2020).
Protein-coding and rRNA variants drive a mitochondrial DNA genotype that associates to low birth weight and is more common in individuals born after assisted reproductive technologies
Authors: Mertens Joke , Belva Florence , Montfoort Aafke van , Zambelli Filippo , Seneca Sara , de Deckersberg Edouard Couvreu , Bonduelle Maryse , Tournaye Herman , Stouffs Katrien , Barbé Kurt , Smeets Hubert , de Velde Hilde Van , Sermon Karen , Blockeel Christophe , Spits Claudia
Published: January 2023

Children born using assisted reproductive technologies (ART) have an increased risk of a lower birth weight, the cause of which remains unclear. As a causative factor, we hypothesized that variants in the mitochondrial DNA (mtDNA) that are not associated with disease, may explain changes in birth weight.
We deep-sequenced the mtDNA of 451 ART and spontaneously conceived (SC) individuals, 157 mother-child pairs and 113 individual oocytes from either natural menstrual cycles or cycles with ovarian stimulation (OS). The mtDNA genotypes were compared across groups and logistic regression and discriminant analysis were used to study the impact of the different factors on birth weight percentile.
ART individuals more frequently carried variants with higher heteroplasmic loads in protein and rRNA-coding regions. These differences in the mitochondrial genome were also predictive of the risk of a lower birth weight percentile, irrespective of the mode of conception but with a sex-dependent culture medium effect. The higher incidence of these variants in ART individuals results both from maternal transmission and de novomutagenesis, which we found not to be caused by OS but to be associated to maternal ageing.
MtDNA variants in protein and rRNA coding regions are associated with a lower birth weight and are more frequently observed in ART children. We propose that these non-disease associated variants can result in a suboptimal mitochondrial function that impacts birth weight. Future research will establish the long-term health consequences of these changes and how these findings will impact the clinical practice and patient counselling in the future.
Reasonable mowing and nitrogen fertilization promote chromium remediation by the hyperaccumulator Leersia hexandra Swartz
Authors: Ma Sairu , Jiang Xusheng , Liu Jie , Ding Zhifan , Dai Demin , Chen Shiqi , Zhao Jingshu
Published: January 2023

Leersia hexandra Swartz, is a chromium (Cr) hyperaccumulator, but the potential for continuous remediation or reasonable mowing and nitrogen fertilization pattern has not been fully characterized. This study aimed to investigate the Cr remediation by L. hexandra under reasonable mowing and nitrogen fertilization patterns using hydroponic experiments. The mowing heights (no mowing, CK; the shoots were reserved for 0, 5 and 10 cm), mowing time (CK; the shoots were mowing after 30, 60, 90 and 120 days), mowing frequencies (CK; the shoots were mowing for 1, 2 and 3 times) and concentrations (42, 84 and 168 mg/L) of nitrogen fertilization (calcium nitrate, ammonium sulfate, and urea) have effects on biomass, Cr concentration and accumulation in shoots of L. hexandra. The results show that the highest biomass (67.0 g) and Cr accumulation (5.33 mg/pot) of L. hexandra found at mowing pattern (10 cm, 90 days, three times), which were increased by 91.4%, and 36.0% compared to CK, respectively. The addition of 84 mg/L ammonium sulfate significantly increased (p < 0.05) the biomass and Cr accumulation of L. hexandra. In addition, the contents of hormones GA3, 6-BA, 6-KT, TZR and JA in leaves were significantly increased under reasonable mowing and nitrogen fertilization treatments, while IPA and JA in stems. In conclusion, the study results have shown that reasonable mowing and nitrogen fertilization are effective options for improving the continuous phytoremediation of Cr-contaminated.
Non-vernalization requirement for flowering in Brassica rapa conferred by a dominant allele of FLOWERING LOCUS T
Authors: Nishikawa Minami , Tamiru Muluneh , Hara Makishi , Segawa Tenta , Saiga Sorachi , Makita Natsu , Itoh Noriaki , Imamura Tomohiro , Sekine Masami , Takagi Hiroki
Published: January 2023

Controlling the timing of flowering is key to improving yield and quality of several agricultural crops including the Brassicas. Many Brassicaceae plants possess a conserved flowering mechanism in which FLOWERING LOCUS C (FLC) represses the transcription of flowering activators, such as FLOWERING LOCUS T (FT), during vernalization. Here, we employed genetic analysis based on next-generation sequencing to identify a dominate FT allele, BrFT2-C, for flowering in the absence of vernalization in the Brassica rapa cultivar ‘CHOY SUM EX CHINA 3’. BrFT2-C harbors two large insertions upstream of its coding region and is constitutively expressed without vernalization, despite FLCexpression. We show that BrFT2-C offers an opportunity to introduce flowering without vernalization requirement into winter-type brassica crops, including B. napus, which have many functional FLC paralogs. Furthermore, we demonstrated the feasibility of using B. rapa harboring BrFT2-C as rootstock for grafting to induce flowering in radish (Raphanus sativus), which requires vernalization for flowering. We believe that the ability of BrFT2-C to overcome repression by FLCcan have significant applications in brassica crops breeding to increase yields by accelerating or delaying flowering.
Comparative analysis of CYP2C8-medidated drug-drug interactions produced by CYP2C8 inhibitors, gemfibrozil versus clopidogrel, focusing on the inhibition of drug distribution in UDP-glucuronosyltransferase prior to oxidation
Authors: Iga Katsumi , Kiriyama Akiko
Published: January 2023

Purpose
It is challenging to predict CYP2C8-mediated drug-drug interactions (DDIs) produced by clopidogrel (Clop) and gemfibrozil (Gem) by maintaining the victim’s fractional CYP2C8-mediated clearance (fm,CYP2C8) constant. The goal is to develop a comprehensive methodology for this.
Method
A model where UDP glucuronosyl transferase (UGT) and CYP work in pairs was devised, under the assumption that CYP2C8 substrates bind UGT before oxidation, and that Gem inhibits UGT and CYP2C8 while Clop inhibits CYP2C8 alone. Overall enzymatic inhibitory activity resulting from DDI was expressed as a function of fm,CYP2C8, fm,UGT (fractional UGT-mediated clearance), and perpetrator specific inhibitory activities against CYP2C8 and UGT (pAi,CYP2C8 and pAi,UGT(d)). Reported DDIs where Clop, Gem, or Gem + itraconazole have victimized montelukast, desloratadine, pioglitazone, repaglinide (OATP1B1 substrate) or cerivastatin (OATP1B1 substrate) were chosen for the analysis. Additionally, a method to simulate the victim’s plasma metabolite levels in response to the changes in the plasma unchanged drug levels was devised based on the previous method.
Results
The changes in the plasma levels of unchanged drug and metabolite produced by the DDIs were simulated successfully. The results confirmed the DDIs were not affected by the hepatic uptake transporter (OATP1B1). The pAi,CYP2C8 values for Clop and Gem were estimated to be 7 (85% inhibition) and 15 (93% inhibition). The pAi,UGT(d) values for Clop and Gem were estimated to be 1 (non-inhibition) and 2 (50% inhibition).
Conclusions
To predict CYP2C8 mediated DDIs, information on the victim’s fm,CYP2C8 and fm,UGT as well as the perpetrator’s pAi,CYP2C8 and pAi,UGT(d) are the most important.
The effectiveness of the MSR in stabilizing EU ETS market and incentivizing low-carbon investment
Authors: Wu Libo , Gong Yanran , Wang Chujun , Tang Weiqi
Published: January 2023

The EU ETS introduced the Market Stability Reserve (MSR) since 2019, to balance out the surplus in its allowances, improve the market stability, and thus, to restore its incentives for low-carbon investments. However, the effectiveness of the MSR is yet to be tested. Taking the Covid-19 pandemic as a social experiment, we prove that the MSR activated a stronger rebound in carbon price by boosting market expectations after the major demand shock, and thus stabilized the European carbon market. But in normal years, the MSR doesn’t have a significant or persistent impact that would break the market stability. We also prove that green-stock indices, as a proxy of incentives for low-carbon investments, are closely related to the carbon price, and the introduction of the MSR improved its resilience to external shocks. The results prove the effectiveness of the MSR and justify the introduction of similar market stabilizing mechanisms in other emission trading schemes.
Perceptions of pre-clerkship students about workplace learning in the clinical learning environment at Gulf Medical University, UAE: An exploratory study.
Authors: Adnan Nooreen , Azhar Farah , Azim Syeda Rubaba
Published: January 2023

Background:
Medical students view clinical workplace placements as an inspiring and motivating learning environment where active student participation is pivotal to development of students’ identity. The progress from pre-clerkship to clerkship education harbours many challenges which consist of experiential learning, adjusting to the clinical environment, and understanding roles & responsibilities. Workplace learning course was recently initiated for pre-clerkship students at a medical university in UAE, which will enable their smooth entry into the clerkship phase of the curriculum.
Objectives
The research aims to explore students’ perceptions of various domains of their clinical learning environment (CLE), highlight the challenges they face, and extract valuable feedback to improve their environment.
Methods:
This study was conducted qualitatively by using focus groups method in order to explore students’ perceptions of the clinical learning environment. Two focus group discussions were conducted (n = 8 +/-10) to determine the common challenges of workplace learning and its potential solutions. Data were analyzed using thematic analysis.
Result:
The focus groups helped to deeply explore the perceptions of students about their clinical learning environment. It helped to reveal the challenges encountered by the students including the significance of proper orientation of staff and students, language barrier, availability of learning opportunities, and supervision quality. The focus groups provided worthwhile suggestions to improve the learning opportunities in the clinical learning environment.
Conclusion:
This study attempted to identify the pre-clerkship students’ perception of their clinical learning environment and the challenges they face over there. Possible suggestions by the students included a formal orientation for the staff and students to be carried out at the beginning. Efforts should be made by clerkship directors to provide students with learning opportunities by increasing patient exposure, encouraging participation, and providing high-quality supervision.
Flexible multi-channel electrodes for acute recording in the non-human primates
Authors: Pei Weihua , Wang Yang , Wang Qifan , Zheng Ruichen , Xu Xinxiu , Yang Xinze , Gui Qiang , Yang Xiaowei , Wang Yijun , Cui He
Published: January 2023

Flexible electrodes have demonstrated good biocompatibility compared to rigid electrodes in relieving encapsulation and long-term recording. The structural and functional properties of the brain in non-human primates are closer to those of humans than in rodents. However, the application of flexible electrodes on non-human primates has been rarely reported. One of the challenges is the long experimental iteration of the electrodes, limited by implanting period, both pre- and post-surgery. In the present study, a flexible multi-channel electrode array for non-human primates was developed and implemented to the extracellular recording in behaving monkeys. To decrease possible risks, a guide-tube-compatible implantation solution was designed to implant electrodes into the cortex without durotomy. Furthermore, packaging and acute recording of multi-channel flexible electrodes for primates were tested ex vivo and in vivo. The results showed that the flexible electrodes and implantation method used in this study meet the needs of extracellular recording in non-human primates. Task-related neuronal activities were recorded with a high signal-to-noise ratio, providing a minimally invasive and clinically viable approach for extracellular recording.
A New Perspective on Tegelbarg. Character and chronology of a Late Neolithic shell midden in the western Baltic
Authors: Kleijne Jos , Huisman Hans
Published: January 2023

The site of Tegelbarg is a Late Neolithic shell midden situated on the Baltic coast in Northern Europe. Spatially and temporally separated from its famous Danish counterparts, it presents an intriguing anomaly in a full-fledged agricultural society. We present a combined perspective on the chronology and the character of this occupation using archaeological soil micromorphology and the Bayesian modelling of radiocarbon dates. The earliest human presence predates the shell midden formation. A coffin grave was dug during the Younger Neolithic, in which a crouched inhumation burial was placed. The Later Neolithic occupants provided a flint dagger to this grave, up to two centuries later, as an act of remembrance. Subsequent settlement activities included the construction of hearths, the production of flint daggers, and the use of coastal resources. The absence of fish bones can be explained by taphonomy, instead of prehistoric subsistence strategies. Landscape changes led to the site’s abandonment and the start of peat development.
Paracentral Acute Middle Maculopathy Presenting as a Sign of Impending Central Retinal Artery Occlusion: A Case Report
Authors: Louie Emily , Tang Anthony , King Benjamin
Published: January 2023

Background: To report a case of paracentral acute middle maculopathy (PAMM) that progressed to central retinal artery occlusion (CRAO) on spectral domain-optical coherence tomography (SD-OCT).
Case Presentation: A 63-year-old male presented with a paracentral scotoma that began several days ago. His past medical history consisted of third degree atrioventricular heart block requiring a pacemaker. Giant cell arteritis was ruled out after erythrocyte sedimentation rate and c-reactive protein levels were normal. SD-OCT revealed a characteristic hyperreflective band in the inner nuclear layer consistent with PAMM in his left eye. Fluorescein angiography was obtained and demonstrated an area of non-perfusion in the parafoveal region. Five days later, the patient developed no light perception in the left eye. SD-OCT showed a diffuse inner retinal hyperreflectivity consistent with CRAO.
Conclusion: PAMM can be a harbinger event for complete CRAO. Complete stroke evaluation should be performed to prevent a cerebrovascular event or progression to complete blindness in the involved eye.
Efficacy and Safety of Dofetilide and Sotalol in Patients With Hypertrophic Cardiomyopathy
Authors: Chen Christopher , Lal Mallika , Burton Yunwoo , Chen Hongya , Stecker Eric , Masri Ahmad , Nazer Babak
Published: January 2023

Background
Professional society practice guidelines conflict regarding their recommendations of dofetilide (DOF) and sotalol (STL) for treatment of arrhythmias in hypertrophic cardiomyopathy (HCM), and supporting data is sparse. We aim to assess safety and efficacy of DOF and STL on arrhythmias in HCM.
Methods
This was an observational study of HCM patients treated with DOF or STL for atrial fibrillation (AF) and ventricular arrhythmias (VA). Outcomes of drug discontinuation and arrhythmia recurrence were compared at 1 year and latest follow-up by Kaplan-Meier analysis. Predictors of drug failure were studied using uni- and multi-variable analyses. Drug-related adverse events were quantitated.
Results
Of our cohort of 72 patients (54 ± 14 years old, 75% male), 21 were prescribed DOF for AF, 52 STL for AF, and 18 STL for VA. At 1 year, discontinuation and recurrence rates were similar for DOF-AF (38% and 43%) and STL-AF (29% and 44%) groups. Efficacy data was similar at long-term follow-up of 1603 (IQR 994–4131) days, and for STL-VA. Drug inefficacy was the most common reason for discontinuation (28%) followed by side-effects (13%). Incidences of heart failure hospitalization (5%) and mortality (3%) were low. One STL-AF patient developed non-sustained torsades de pointes in the setting of severe pneumonia and acute kidney injury, but there were no other drug-related serious adverse events.
Conclusion
DOF and STL demonstrate moderate efficacy and excellent safety when used for AF and VA in HCM patients.
Barriers and facilitators of health self-management for the managers in long-term care facilities—a qualitative exploration based on Theoretical Domains Frame
Authors: Huang Li-Li , Guan Xian-Hua , Hu Wei-Wei , Jiang Yan-Hong , Fu Jing-Jing , Hong Wei-Wen
Published: January 2023

Background: Long-term care development has become a global demand. Nurse directors play a crucial role in managing a long-term care facility's quality and costs. In terms of health self-management, they face many challenges. Health self-
management of nursing service quality managers, however, is relatively unknown.
Methods: An interview outline were developed based on the framework of theoretical domains. 17 managers were selected for semistructured interviews using purposeful sampling and the snowball method. Nurses, nursing managers, and nursing directors participated in this study. Content analysis was conducted using transcripts of interview recordings, interview notes, reflection diaries, and other materials.
Results: Data saturation was reached after the 17th face-to-face interview. Five barriers topics and related sub-topics were categorised in ten domains of the Theoretical Domains Framework. The main barriers to healthy self-management were: (1)Negative emotional influence, (2) Limited time resources, (3) Fetters from professional roles, (4) Lack of positive reinforcement, (5) Concerns about physical red flags. In the ten TDF domains, six facilitators topics and related sub-themes were also identified. These key facilitators included: (1) Highlight the benefits of good habits, (2) Intention to balance life and work, (3) The impact of being considered a benchmark, (4) Fragmented exercise management, (5) Find the team, (6)Wear sports electronic equipment.
Conclusion: This study identified a wide range of barriers and facilitators of self-healthy behaviors in long-term care facilities. Managers may consider whether these barriers and facilitators operate in their work. To promote health self-management, provide ideas and references for future research.
Using computer-based habit versus chess-based cognitive remediation training as add-on therapy to modify the imbalance between habitual behavior and cognitive control in tobacco use disorder: protocol of a randomized controlled, fMRI study
Authors: Karl Damian , Wieland Alfred , Shevchenko Yury , Grundinger Nadja , Machunze Noah , Gerhardt Sarah , Flor Herta , Vollstädt-Klein Sabine
Published: January 2023

Background:
Although the vast majority of smokers are aware of the enormous preventable health hazards caused by smoking, only a small percentage of smokers manage to remain abstinent in the long term. One possible explanation for this discrepancy lies in the inflexibility of addictive behavior and associated disadvantageous decision‐making. According to a dual‐process theory of decision‐making, two distinct decision systems can be identified. One slow deliberate system based on desirable expectations of outcome value described as goal‐directed behavior and a fast reflexive system based on habitual instrumental behavior and driven by reinforcement experienced in the past. In the course of addiction development, an imbalance occurs between habitual behavior and goal-directed. The present study aims to investigate the modifiability of the balance between habitual and goal-directed behavior at the neurobiological and behavioral level in smokers using two different novel add-on therapies. We hypothesize that both interventions change the balance between goal-directed and habitual behavior, but by different mechanisms. Whereas a cognitive remediation treatment should directly improve cognitive control, in contrast an implicit priming task should affect the early processing and the emotional valence of smoking and smoking cues.
Methods:
We will conduct a randomized controlled study in treatment-seeking individuals with tobacco use disorder applying either chess-based cognitive remediation training (N = 30) or implicit computer-based habit-modifying training (N = 30) as add on therapy compared to the standard smoking cessation group therapy (N = 30) only. We will address neurobiological and neuropsychological correlates associated with craving, reward devaluation, cue reactivity and attentional bias. In addition, various effects of treatment and prediction of treatment outcome will be examined using behavioral and neural measures.
Discussion: The present study will apply different examination methods such as functional magnetic resonance imaging, neuropsychological tests, and self-report before and after the interventions. This allows the identification of intervention-specific mechanisms and therefore potential neurobiology-based specific treatment targets for individuals with Tobacco Use Disorder.
Trial registration: Registered at clinicaltrials.gov/ct2/show/NCT03764969 (05 December 2018).
Massive airway hemorrhage in severe COVID-19 and the role endotracheal tube clamping
Authors: guo litao , Liu Yu , Zhang Lei , Li Qing , Qiu Haibo , Guo Yaling , Shi Qindong
Published: January 2023

Background
Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been widely used in treating patients with coronavirus disease 2019 (COVID-19) with severe respiratory failure. However, there are few reports of the successful treatment of patients with massive airway hemorrhage in severe COVID-19 during VV-ECMO treatment.
Methods
We analyzed the treatment process of a patient with massive airway hemorrhage in severe COVID-19, who underwent prolonged VV-ECMO treatment.
Results
A 59-year-old female patient was admitted to the intensive care unit after confirmed severe acute respiratory syndrome coronavirus 2 infection with severe acute respiratory distress syndrome. VV-ECMO, mechanical ventilation and prone ventilation were administered. Major airway hemorrhage occurred on day 14 of ECMO treatment; conventional management was ineffective. We provided complete VV-ECMO support, discontinued anticoagulation, disconnected the ventilator, clipped the tracheal intubation, and intervened to embolize the descending bronchial arteries. After the pulmonary pemorrhage stopped, we administered cryotherapy under bronchoscopy, low-dose urokinase locally, and bronchoalveolar lavage in the airway to clear the blood clots. The patient’s condition gradually improved; she underwent ECMO weaning and decannulation after 88 days of VV-ECMO treatment, and the membrane oxygenator was changed out four times. She was successfully discharged after 182 days in hospital.
Conclusion
Massive airway hemorrhage in patients with severe COVID-19 and treated with ECMO is catastrophic. It is feasible to clamp the tracheal tube with the full support of ECMO. Notably, bronchoscopy with cryotherapy is effective for removing blood clots.