bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicentre, patient- and assessor-blinded, non-inferiority, randomised and controlled phase II trial to compare standard and torque teno virus-guided immunosuppression in kidney transplant recipients in the first year after transplantation: TTVguideIT
Authors: Haupenthal Frederik , Rahn Jette , Maggi Fabrizio , Gelas Fanny , Bourgeois Philippe , Hugo Christian , Jilma Bernd , Böhmig Georg A. , Herkner Harald , Wolzt Michael , Doberer Konstantin , Vossen Matthias , Focosi Daniele , Neuwirt Hannes , Banas Miriam , Banas Bernhard , Budde Klemens , Viklicky Ondrej , Malvezzi Paolo , Rostaing Lionel , Rotmans Joris I. , Bakker Stephan J. L. , Eller Kathrin , Cejka Daniel , Pérez Alberto Molina , Rodriguez-Arias David , König Franz , Bond Gregor ,   the TTVguideTX consortium partners, Melzer Georg , del Alamo Martha , Beneyto Isabel , Navarro David , Ohlmann Sophie 
Published: March 2023

Abstract
Background
Immunosuppression after kidney transplantation is mainly guided via plasma tacrolimus trough level, which cannot sufficiently predict allograft rejection and infection. The plasma load of the non-pathogenic and highly prevalent torque teno virus (TTV) is associated with the immunosuppression of its host. Non-interventional studies suggest the use of TTV load to predict allograft rejection and infection. The primary objective of the current trial is to demonstrate the safety, tolerability and preliminary efficacy of TTV-guided immunosuppression.

Methods
For this purpose, a randomised, controlled, interventional, two-arm, non-inferiority, patient- and assessor-blinded, investigator-driven phase II trial was designed. A total of 260 stable, low-immunological-risk adult recipients of a kidney graft with tacrolimus-based immunosuppression and TTV infection after month 3 post-transplantation will be recruited in 13 academic centres in six European countries. Subjects will be randomised in a 1:1 ratio (allocation concealment) to receive tacrolimus either guided by TTV load or according to the local centre standard for 9 months. The primary composite endpoint includes the occurrence of infections, biopsy-proven allograft rejection, graft loss, or death. The main secondary endpoints include estimated glomerular filtration rate, graft rejection detected by protocol biopsy at month 12 post-transplantation (including molecular microscopy), development of de novo donor-specific antibodies, health-related quality of life, and drug adherence. In parallel, a comprehensive biobank will be established including plasma, serum, urine and whole blood. The date of the first enrolment was August 2022 and the planned end is April 2025.

Discussion
The assessment of individual kidney transplant recipient immune function might enable clinicians to personalise immunosuppression, thereby reducing infection and rejection. Moreover, the trial might act as a proof of principle for TTV-guided immunosuppression and thus pave the way for broader clinical applications, including as guidance for immune modulators or disease-modifying agents.

Trial registration
EU CT-Number: 2022-500024-30-00
Comparing the effects of smartphone-based and face-to-face pulmonary rehabilitation education on caregiver burden and quality of life among the family caregivers of patients with chronic obstructive pulmonary disease: a randomized controlled field trial
Authors: Bahadori Mobina , Sami Ramin , Abolhassani Shahla , Atashi Vajihe 
Published: March 2023

Abstract
Background
Functional limitation among patients with chronic obstructive pulmonary disorder (COPD) and their dependence on their family caregivers (FCs) can significantly increase caregiver burden (CB) and reduce the quality of life (QOL) among FCs. Education of pulmonary rehabilitation (PR) to FCs is a strategy with potential positive effects on CB. This study was conducted to compare the effects of smartphone-based and face-to-face (FTF) PR education on CB and QOL among the FCs of patients with COPD.

Methods
This randomized controlled field trial was conducted in 2021–2022. Participants were purposefully selected from the PR unit of Khorshid comprehensive respiratory care clinic in Isfahan, Iran, and randomly allocated to a control and an intervention group. Participants in the control group received PR education in twelve 30–60-min FTF sessions held twice weekly in six consecutive weeks. Their counterparts in the intervention group received PR education for 6 weeks through an android application. The Zarit Burden Interview and the 12-item Short Form Health Survey (SF-12) were used for data collection before and immediately after the study intervention. The SPSS software (v. 24.0) was used to analyze the data through the independent-sample t, paired-sample t, chi-square, and Fisher’s exact tests.

Results
The means of participants’ age was 47.7 ± 13.8 years in the control group and 44.1 ± 14.8 years in the intervention group. Most participants in these groups were female (82.9% vs. 71.4%). The pretest mean scores of CB and QOL were respectively 50.77 ± 10.64 and 27.82 ± 3.9 in the control group and 49.77 ± 7.65 and 26.71 ± 3.5 in the intervention group with no significant between-group difference (P > 0.05). At the posttest, these values were respectively 51.57 ± 7.32 and 27.74 ± 3.28 in the control group and 37.31 ± 6.95 and 34.37 ± 2.8 in the intervention group, and between-group differences were significant (P < 0.05). The mean scores of CB and QOL did not significantly change in the control group (P > 0.05), but respectively decreased and increased significantly in the intervention group (P < 0.05).

Conclusions
Smartphone-based PR education is effective in significantly decreasing CB and improving QOL among the FCs of patients with COPD.

Trial registration
Iranian Registry of Clinical Trials IRCT20161203031200N3
Diabetic kidney disease induces transcriptome alterations associated with angiogenesis activity in human mesenchymal stromal cells
Authors: Bian Xiaohui , Conley Sabena M. , Eirin Alfonso , Zimmerman Zuckerman Eric A. , Smith Anastasia L. , Gowan Cody C. , Snow Zachary K. , Jarmi Tambi , Farres Houssam , Erben Young M. , Hakaim Albert G. , Dietz Matthew A. , Zubair Abba C. , Wyles Saranya P. , Wolfram Joy V. , Lerman Lilach O. , Hickson LaTonya J. 
Published: March 2023

Abstract
Background
Therapeutic interventions that optimize angiogenic activities may reduce rates of end-stage kidney disease, critical limb ischemia, and lower extremity amputations in individuals with diabetic kidney disease (DKD). Infusion of autologous mesenchymal stromal cells (MSC) is a promising novel therapy to rejuvenate vascular integrity. However, DKD-related factors, including hyperglycemia and uremia, might alter MSC angiogenic repair capacity in an autologous treatment approach.

Methods
To explore the angiogenic activity of MSC in DKD, the transcriptome of adipose tissue-derived MSC obtained from DKD subjects was compared to age-matched controls without diabetes or kidney impairment. Next-generation RNA sequencing (RNA-seq) was performed on MSC (DKD n = 29; Controls n = 9) to identify differentially expressed (DE; adjusted p < 0.05, |log2fold change|> 1) messenger RNA (mRNA) and microRNA (miRNA) involved in angiogenesis (GeneCards). Paracrine-mediated angiogenic repair capacity of MSC conditioned medium (MSCcm) was assessed in vitro using human umbilical vein endothelial cells incubated in high glucose and indoxyl sulfate for a hyperglycemic, uremic state.

Results
RNA-seq analyses revealed 133 DE mRNAs (77 upregulated and 56 down-regulated) and 208 DE miRNAs (119 up- and 89 down-regulated) in DKD-MSC versus Control-MSC. Interestingly, miRNA let-7a-5p, which regulates angiogenesis and participates in DKD pathogenesis, interacted with 5 angiogenesis-associated mRNAs (transgelin/TAGLN, thrombospondin 1/THBS1, lysyl oxidase-like 4/LOXL4, collagen 4A1/COL4A1 and collagen 8A1/COL8A1). DKD-MSCcm incubation with injured endothelial cells improved tube formation capacity, enhanced migration, reduced adhesion molecules E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 mRNA expression in endothelial cells. Moreover, angiogenic repair effects did not differ between treatment groups (DKD-MSCcm vs. Control-MSCcm).

Conclusions
MSC from individuals with DKD show angiogenic transcriptome alterations compared to age-matched controls. However, angiogenic repair potential may be preserved, supporting autologous MSC interventions to treat conditions requiring enhanced angiogenic activities such as DKD, diabetic foot ulcers, and critical limb ischemia.
Effect of phage vB_EcoM_FJ1 on the reduction of ETEC O9:H9 infection in a neonatal pig cell line
Authors: Ferreira Alice , Silva Daniela , Almeida Carina , Rodrigues Maria Elisa , Silva Sónia , Castro Joana , Mil-Homens Dalila , García-Meniño Isidro , Mora Azucena , Henriques Mariana , Oliveira Ana 
Published: March 2023

AbstractEnterotoxigenic Escherichia coli (ETEC) colonizes the intestine of young pigs causing severe diarrhoea and consequently bringing high production costs. The rise of antibiotic selective pressure together with ongoing limitations on their use, demands new strategies to tackle this pathology. The pertinence of using bacteriophages as an alternative is being explored, and in this work, the efficacy of phage vB_EcoM_FJ1 (FJ1) in reducing the load of ETEC EC43-Ph (serotype O9:H9 expressing the enterotoxin STa and two adhesins F5 and F41) was assessed. Foreseeing the oral application on piglets, FJ1 was encapsulated on calcium carbonate and alginate microparticles, thus preventing phage release under adverse conditions of the simulated gastric fluid (pH 3.0) and allowing phage availability in simulated intestinal fluid (pH 6.5). A single dose of encapsulated FJ1, provided to IPEC-1 cultured cells (from intestinal epithelium of piglets) previously infected by EC43, provided bacterial reductions of about 99.9% after 6 h. Although bacteriophage-insensitive mutants (BIMs) have emerged from treatment, the consequent fitness costs associated with this new phenotype were demonstrated, comparatively to the originating strain. The higher competence of the pig complement system to decrease BIMs’ viability, the lower level of colonization of IPEC-1 cells observed with these mutants, and the increased survival rates and health index recorded in infected Galleria mellonella larvae supported this observation. Most of all, FJ1 established a proof-of-concept of the efficiency of phages to fight against ETEC in piglet intestinal cells.
Co-occurrence network analysis unveils the actual differential impact on the olive root microbiota by two Verticillium wilt biocontrol rhizobacteria
Authors: Cardoni Martina , Fernández-González Antonio J. , Valverde-Corredor Antonio , Fernández-López Manuel , Mercado-Blanco Jesús 
Published: March 2023

Abstract
Background
Verticillium wilt of olive (VWO), caused by Verticillium dahliae Kleb, is one of the most threatening diseases affecting olive cultivation. An integrated disease management strategy is recommended for the effective control of VWO. Within this framework, the use of biological control agents (BCAs) is a sustainable and environmentally friendly approach. No studies are available on the impact that the introduction of BCAs has on the resident microbiota of olive roots. Pseudomonas simiae PICF7 and Paenibacillus polymyxa PIC73 are two BCAs effective against VWO. We examined the effects of the introduction of these BCAs on the structure, composition and co-occurrence networks of the olive (cv. Picual) root-associated microbial communities. The consequences of the subsequent inoculation with V. dahliae on BCA-treated plants were also assessed.

Results
Inoculation with any of the BCAs did not produce significant changes in the structure or the taxonomic composition of the ‘Picual’ root-associated microbiota. However, significant and distinctive alterations were observed in the topologies of the co-occurrence networks. The introduction of PIC73 provoked a diminution of positive interactions within the ‘Picual’ microbial community; instead, PICF7 inoculation increased the microbiota’s compartmentalization. Upon pathogen inoculation, the network of PIC73-treated plants decreased the number of interactions and showed a switch of keystone species, including taxa belonging to minor abundant phyla (Chloroflexi and Planctomycetes). Conversely, the inoculation of V. dahliae in PICF7-treated plants significantly increased the complexity of the network and the number of links among their modules, suggestive of a more stable network. No changes in their keystone taxa were detected.

Conclusion
The absence of significant modifications on the structure and composition of the ‘Picual’ belowground microbiota due to the introduction of the tested BCAs underlines the low/null environmental impact of these rhizobacteria. These findings may have important practical consequences regarding future field applications of these BCAs. Furthermore, each BCA altered the interactions among the components of the olive belowground microbiota in idiosyncratic ways (i.e. PIC73 strongly modified the number of positive relations in the ‘Picual’ microbiota whereas PICF7 mostly affected the network stability). These modifications may provide clues on the biocontrol strategies used by these BCAs.
Feasibility indicators in obesity-related behavioral intervention preliminary studies: a historical scoping review
Authors: Pfledderer Christopher D. , von Klinggraeff Lauren , Burkart Sarah , Wolfenden Luke , Ioannidis John P. A. , Beets Michael W. 
Published: March 2023

Abstract
Background
Behavioral interventions are often complex, operate at multiple levels, across settings, and employ a range of behavior change techniques. Collecting and reporting key indicators of initial trial and intervention feasibility is essential to decisions for progressing to larger-scale trials. The extent of reporting on feasibility indicators and how this may have changed over time is unknown. The aims of this study were to (1) conduct a historical scoping review of the reporting of feasibility indicators in behavioral pilot/feasibility studies related to obesity published through 2020, and (2) describe trends in the amount and type of feasibility indicators reported in studies published across three time periods: 1982–2006, 2011–2013, and 2018–2020.

Methods
A search of online databases (PubMed, Embase, EBSCOhost, Web of Science) for health behavior pilot/feasibility studies related to obesity published up to 12/31/2020 was conducted and a random sample of 600 studies, 200 from each of the three timepoints (1982–2006, 2011–2013, and 2018–2020), was included in this review. The presence/absence of feasibility indicators, including recruitment, retention, participant acceptability, attendance, compliance, and fidelity, were identified/coded for each study. Univariate logistic regression models were employed to assess changes in the reporting of feasibility indicators across time.

Results
A total of 16,365 unique articles were identified of which 6873 of these were reviewed to arrive at the final sample of 600 studies. For the total sample, 428 (71.3%) studies provided recruitment information, 595 (99.2%) provided retention information, 219 (36.5%) reported quantitative acceptability outcomes, 157 (26.2%) reported qualitative acceptability outcomes, 199 (33.2%) reported attendance, 187 (31.2%) reported participant compliance, 23 (3.8%) reported cost information, and 85 (14.2%) reported treatment fidelity outcomes. When compared to the Early Group (1982–2006), studies in the Late Group (2018–2020) were more likely to report recruitment information (OR=1.60, 95%CI 1.03–2.49), acceptability-related quantitative (OR=2.68, 95%CI 1.76–4.08) and qualitative (OR=2.32, 95%CI 1.48–3.65) outcomes, compliance outcomes (OR=2.29, 95%CI 1.49–3.52), and fidelity outcomes (OR=2.13, 95%CI 1.21, 3.77).

Conclusion
The reporting of feasibility indicators within behavioral pilot/feasibility studies has improved across time, but key aspects of feasibility, such as fidelity, are still not reported in the majority of studies. Given the importance of behavioral intervention pilot/feasibility studies in the translational science spectrum, there is a need for improving the reporting of feasibility indicators.
Screening of indigenous actinobacteria as biological control agents of Colletotrichum capsici and increasing chili production
Authors: Yanti Yulmira , Hamid Hasmiandy , Reflin  , Yaherwandi  , Nurbailis  , Suriani Ni Luh , Reddy M. S. , Syahputri Mila 
Published: March 2023

AbstractBackgroundAnthracnose disease caused byColletotrichum capsiciis a major disease in chili plants that is difficult to control. Actinobacteria have potential biological control agents forC. capsicibecause of their antifungal properties and dominant presence in soil. The study aimed to obtain actinobacteria isolates that have the potential to control anthracnose in planta and increase the growth and production of chili plants. The study consisted of three stages: isolation, selection, and characterization of the best actinobacteria isolates. A total of 20 isolates of indigenous actinobacteria were isolated, and 16 isolates were successfully selected based on the results of the biosafety test.ResultsThein plantatest showed that eight isolates could control anthracnose with 100% effectiveness. Of the eight isolates, as many as five players increased the production of chili plants by 169.51–218.53 g. Actinobacterial isolates that have the potential to control anthracnose diseasein plantaand increase the growth and production of chili plants are ARAI 3221, ARAC 3221, ARAC 2211, ARAC 3321, and ARTI 1312. These isolates produced indole acetic acid (IAA) with concentrations of 25.82–88.87 ppm, and four isolates were able to dissolve phosphate. Five isolates produced chitinase enzyme with the chitinolytic index of 0.32–1.78.ConclusionThe introduction of actinobacteria in chili plants was also proven to extend the incubation period, reduce the incidence of disease, and reduce the severity of anthracnose disease compared to negative controls and mancozeb. Actinobacteria can suppress pathogenic microorganisms that can inhibit plant growth. Actinobacteria have the potential to increase the growth and production of chili plants. The results of 16S rRNA sequences showed that the five potential isolates were identified asStreptomyces cellulose,S.fradiae,S.olivaceus,S.pseudogriseolus﻿,andS.griseoflavus.
Long-Term Disproportional TSH Hyposecretion in a Patient With Nonautoimmune Hyperthyroidism After Radioiodine Therapy
Authors: Nishihara Eijun , Fukata Shuji , Miyauchi Akira , Akamizu Takashi 
Published: March 2023

Abstract
Nonautoimmune hyperthyroidism (NAH), caused by constitutively active mutants of the thyrotropin receptor (TSHR) gene, is recommended to be treated with total thyroidectomy followed by radioiodine administration. Herein, we present a 39-year-old woman with sporadic NAH caused by a TSHR-L512Q mutation. At the age of 20 years, she presented with a large goiter of 370 mL, treated with thiamazole, and opted for radioiodine therapy as outpatient management. Over the next 17 years, she underwent 6 treatments of 13 mCi radioiodine each. She did not experience a relapse of hyperthyroidism, and thiamazole was reduced and later withdrawn during the final radioiodine treatment. The patient's goiter significantly reduced to 18 mL, and thyroid function tests showed that free thyroxine and free triiodothyronine levels were below the lower limit of the reference ranges, while TSH remained within the reference range for 20 months. Along with an almost normal TSH response to thyrotropin-releasing hormone stimulation, no pituitary atrophy was observed on magnetic resonance imaging. Contrary to the recommended treatment, this case showed that fractionated radioiodine therapy alone is effective in controlling thyroid function and in reducing goiter size. Low TSH levels during treatment should not be assessed as subclinical hyperthyroidism or as risk of relapse.
Alfaxalone Alleviates Neurotoxicity and Cognitive Impairment Induced by Isoflurane Anesthesia in Offspring Rats
Authors: Zhao Xingkai , Li Zhendong , Guo Yizhe , Liu Qi , Qing Mengshi , Sheng Yuhan , Chen Ying , Xie Luolan , Zhou Zhenlei 
Published: March 2023

BACKGROUND:
The anesthetic isoflurane can cause neurotoxicity in fetuses and offspring of rats, affecting their neurodevelopment. However, the underlying mechanisms and therapeutic targets of isoflurane-induced neurotoxicity remain to be identified. Alfaxalone (ALF) is a steroid anesthetic. Steroids have been reported to have neuroprotective effects. This study aimed to investigate whether ALF could alleviate the isoflurane-induced neurotoxicity in fetuses and offspring of rats.

METHODS:
On gestation day 15 (G15), the pregnant SD rats were randomly assigned to 4 groups: control 1 (CTL1) + control 2 (CTL2), isoflurane (ISO) + CTL2, CTL1 + ALF, and ISO + ALF. To analyze the changes in the expression levels of inflammatory cytokines, apoptotic factors, and synaptophysin, the brain tissues from the G15 fetuses and offspring at postnatal day 7 (P7), postnatal day 14 (P14), and postnatal day 31 (P31) were collected. The newborn neurons in the rats’ offspring at P7, P14, and P31 were counted using immunofluorescence techniques. The Morris water maze (MWM) test was performed to assess the learning and memory abilities of P31 offspring rats.

RESULTS:
ALF significantly alleviated the isoflurane-induced increase in the expression levels of inflammatory cytokines and apoptotic factors, such as interleukin (IL)-6 (ISO + CTL2 versus ISO + ALF: 5.133 ± 0.739 versus 1.093 ± 0.213, P < .001) and Caspase-3 (6.457 ± 0.6 versus 1.062 ± 0.1, P < .001) in the G15 fetuses. In P31 offspring rats, the expression levels of synaptophysin (0.719 ± 0.04 versus 1.068 ± 0.072, P < .001) and the number of newborn neurons in the dentate gyrus of the hippocampus were significantly lower in the ISO + CTL2 group as compared to those in the ISO + ALF group (118 ± 6 versus 140 ± 7, P < .001). These changes also occurred in the rat offspring at P7 and P14. In the MWM test, the escape latency of CTL1 + ALF group rats was significantly lower than that of ISO + ALF group rats (41 ± 6 versus 31 ± 7, P < .001) at P31.

CONCLUSIONS:
Based on these findings, this study suggested that isoflurane exposure during pregnancy in rats could cause neuroinflammation and death of embryos as well as impairment of cognitive function in the offspring rats. ALF can be used to counteract the negative effects of isoflurane.