bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnitude of depression and associated risk factors among patients with musculoskeletal disorder treated in physiotherapy outpatient department in Amhara region comprehensive specialized hospital in Ethiopia: a prospective cross-sectional study
Authors: Yalew Ermias Solomon , Melese Ashenafi Zemed , Guadie Yisak Girma , Abich Yohannes , Kassa Tesfa , Gashaw Moges
Published: March 2023

Background

The state of depression that can lead to substance and drug abuse, as well as an increased risk of suicide. Without a doubt, the link between musculoskeletal pain and depression compromises a person’s health and drastically lowers their quality of life, resulting in increased incapacity. Depression and musculoskeletal discomfort are two well-known risk factors for long-term sickness absence, which is defined as a period of sickness lasting more than a week, which means chronic musculoskeletal pains, particularly multiple pains, are linked to depression. And early diagnosis and care of depression in musculoskeletal disorder are critical to patients’ physical, functional, and occupational results. This study aimed to assess the magnitude of depression and associated risk factors among patients with musculoskeletal disorder.

Method

Multi-institution cross-sectional study conducted in Amhara region Comprehensive specialized Hospitals from April 1st to May 30th, 2021. The data was collected from 217 participants through interview administrative questioner and patient medical record review. Binary logistic regression was used to identify associated risk factors of depression. The strength of the association was detected by the adjusted odds ratio.

Result

A total of 217 participate in this study with the age range of 18–80 years. Among the study participants, 57.1% (n = 124) (AOR: 95% CI: 50.7–63.6) were had depression. Treatment duration, and social support were significantly association with depression among patient with musculoskeletal disorder with P < 0.05.

Conclusion

The magnitude of depression was relatively high among musculoskeletal disorder patients treated in physiotherapy out-patient department. The length of treatment duration (hospital stay) and the status of social support from families and friends were significantly associated with depression among patients with musculoskeletal disorders. A multidisciplinary strategy is required for diagnosing and treating depression in patients with musculoskeletal disorder.
Depression, anxiety, stress, and PTSD symptoms during the first and second COVID-19 waves: a comparison of elderly, middle-aged, and young people in Iran
Authors: Pasha Hajar , Omidvar Shabnam , Faramarzi Mahbobeh , Bakhtiari Afsaneh
Published: March 2023

Background

A widespread outbreak of epidemics like Covid-19 is a lethal threat to physical and mental health. Recent studies reported a higher prevalence of mental problems in younger individuals, contrary to the general assumption expected in older people. Therefore, it is necessary to compare anxiety, stress, depression and PTSD (post-traumatic stress disorder) symptoms in different age groups during the Covid-19 crisis.

Methods

A cross-sectional online survey was performed (from Dec. 2020 to Feb. 2021) on three age groups of elderly, middle-aged and young people. Data were collected by DASS-21 (Depression, Anxiety and Stress Scale) and IES-R (Impact of Event Revised Scale) and analyzed using ANOVA, χ2 test and logistic regression analysis.

Results

Overall, 601 participants completed the questionnaires, including 23.3% of the elderly (≥ 60 years), 29.5% of the young (18–29 years) and 47.3% of the middle-aged (30–59 years) with 71.4% of women. The logistic regression analysis revealed that the risk of PTSD in young people was higher than in the elderly (β = 2.242, CI: 1.03–4.87, P = 0.041), while the risk of depression, anxiety and stress did not differ significantly among the three age groups. Female gender, occupation, lower economic status, solitary life, and chronic disease were risk factors for psychological symptoms during the Covid-19 pandemic.

Conclusion

Findings on the higher odds ratio of PTSD symptoms in younger individuals have interestingly potential implications to meet the needs of mental health services during Covid-19.
Peripheral blood eosinophilia in adult asthmatic patients and its association with the severity of asthma
Authors: Solomon Yenealem , Malkamu Birhanemaskal , Berhan Ayenew , Eyayu Tahir , Almaw Andargachew , Legese Biruk , Woldu Berhanu
Published: March 2023

Background

Asthma is a diverse disease with various etiologic bases. Severe asthma can be associated with increased mortality, hospitalization, and decreased quality of life for asthma patients. High blood eosinophil counts were associated with severe asthma, but recent studies have failed to confirm this as a marker of severe asthma among adult asthma patients. As a result, the purpose of this study was to determine the association between the severity of asthma and high blood eosinophil count.

Methodology

A simple random sampling technique was used to select 291 asthmatic patients for an institution-based cross-sectional study. Socio-demographic, behavioral, and clinical characteristics were collected by using a pre-tested structured questionnaire. Four milliliters of venous blood were collected from asthmatic patients for complete blood count and peripheral morphology assessment. The eosinophil count was analyzed by the Unicel DxH 800 (Beckman Coulter, Ireland) analyzer. A statistical package for social science version 20 (SPSS) software was used to analyze the data. The non-parametric (Mann-Whitney U) test was used to compare the eosinophil count with different background variables. A binary logistic regression analysis was used to assess the factors associated with eosinophilia. A p-value less than 0.05 in multivariable logistic regression analysis was considered statistically significant.

Result

In this study, the overall magnitude of eosinophilia was 19.6% (95% CI = 14.8–24.1). Being admitted to the emergency department (AOR = 0.25; 95% CI: 0.09–0.69, p = 0.007) and being female (AOR = 0.49; 95% CI: 0.26–0.9, p = 0.025) were shown to have a statistically significant association with eosinophilia. Moreover, the absolute eosinophil count was significantly higher among asthmatic patients infected with intestinal parasitic infection (p < 0.045).

Conclusion

Being female and admission to the emergency department were negatively associated with eosinophilia. Lack of eosinophilia can be related to the low-T2 asthma phenotype. The absolute eosinophil counts were higher among intestinal parasite-infected patients. Therefore, different biomarkers will be considered for the proper diagnosis and management of adult asthma patients.
Musculoskeletal pains among amateur and professional athletes of five disciplines in Senegal: a preliminary study
Authors: Malam Moussa Ahmet Hassane , Bika Lele Elysée Claude , Guessogo Wiliam Richard , Bian Wiliam Mbang , Guyot Jessica , Ahmadou  , Assomo-Ndemba Peguy Brice , Ayina Clarisse Noel , Kojom Foko Loick Pradel , Dupré Caroline , Barth Nathalie , Bongue Bienvenu , Ba Abdoulaye , Samb Abdoulaye , Mandengue Samuel Honoré , Mekoulou Ndongo Jerson
Published: March 2023

Background

Musculoskeletal pains (MSPs) in sport are cause of poor performances and loss of competition in athletes. The present study aimed at determining the prevalence of MSPs with regard to sport disciplines and athletic status.

Methods

A cross-sectional study was conducted among 320 Senegalese professional and amateur athletes practicing football, basketball, rugby, tennis, athletics, and wrestling. Rates of MSPs in the past year (MSPs-12) and week (MSPs-7d) were assessed using standard questionnaires.

Results

Overall proportions of MSPs-12 and MSPs-7d were 70 and 74.2%, respectively. MSPs-12 were more frequently reported on shoulders (40.6%), neck (37.1%) and hips/thigh (34.4%), while MSPs-7d were predominant on hips/thigh (29.5%), shoulders (25.7%), and upper back (17.2%). Proportions of MSPs-12 and MSPs-7d varied significantly by sport disciplines, with highest values among basketball players. Again, highest MSPs-12 proportions on shoulders (29.7%, P = 0.02), wrists/hands (34.6%, P = 0.001), (40.2%, P = 0.0002), and knees (38.8%, P = 0.002) were seen among basketball players. High proportions of MSPs-7d were seen on shoulders (29.6%, P = 0.04) for tennis players, wrists/hands (29.4%, P = 0.03) for basketball and football players, and hips/thigh (38.8%, P < 0.00001) for basketball players. Football players had reduced risk of MSPs-12 by 75% on lower back (OR = 0.25; 95% CI. 0.10—0.63; P = 0.003) and by 72% on knees (OR = 0.28; 95% CI. 0.08—0. 95; P = 0.04). In contrast, tennis players were more at risk of MSPs-12 on shoulders (OR = 3.14; 95% CI. 1.14–8.68; P = 0.02), wrists/hands (OR = 5.18; 95% CI.1.40–11.13; P = 0.01), and hips/thigh (OR = 2.90; 95% CI. 1.1–8.38; P = 0.04). Professionals were protected from MSPs-12 on neck pain with a significant reduction of risk by 61% (OR = 0.39, 95% CI. 0.21–0.75, P = 0.03).

Conclusion

MSPs are a reality among athletes and their risk is modulated by sport disciplines, athletic status and gender.
Chronology of permanent teeth mineralization in Brazilian individuals: age estimation tables
Authors: Kuhnen Barbara , Fernandes Clemente Maia da Silva , Barros Franciéllen de , Scarso Filho José , Gonçalves Marcelo , Serra Mônica da Costa
Published: March 2023

Background

Age is important in forming the uniqueness of individuals. When chronological age is not available, age estimation is required, particularly in court cases. The mineralization chronology of permanent teeth is a valuable tool for age estimation of subadults. This study aimed to evaluate the mineralization stages of permanent teeth of Brazilian subjects from imaging exams, using the classification by Moorrees et al. modified by the authors, to verify the existence of correlation between the chronology of mineralization stages and sex and to prepare numerical tables of the chronology of dental mineralization stages for Brazilian individuals.

Methods

Digital panoramic radiographs of 1100 living Brazilian individuals of both sexes, aged between 2 and 25 years, born between 1990 and 2018, from the image bank of a Dental Radiographs and Documentations clinic located in the city of Araraquara, SP, Brazil. The images were evaluated according to the level of crown and root development and classified according to the stages proposed by Moorrees et al. (Am J Phys Anthropol 21: 205–213, 1963) adapted by the authors. All analyses were performed in the R software. Descriptive and exploratory analyses were performed on all data. For intra- and inter-examiner analyses, the rate of agreement and Kappa statistics at a 95% confidence interval were used. Kappa was interpreted according to Landis and Koch.

Results

Only upper and lower canines showed significant differences between the sexes (p < 0.05), with higher average ages for men. The findings were presented in tables, as well as age estimates with 95% confidence intervals for each mineralization stage and each tooth.

Conclusion

In the present study, we evaluated the mineralization stages of permanent teeth of Brazilian subjects from digital panoramic radiographs and found no correlation between the chronology of mineralization stages and sex, except for canines. From the obtained results, numerical tables of the chronology of dental mineralization stages were prepared.
Regenerative endodontic therapy in mature teeth with necrotic pulp and apical periodontitis using two disinfection protocols
Authors: Eldessoky Aalaa E. , Khalefa Mohammed M. , Abu-Seida Ashraf M.
Published: March 2023

Objective

This study compared the effect of diode laser (DL) 980 nm and double antibiotic paste (DAP) on response of mature teeth with necrotic pulp and apical periodontitis to regenerative endodontic therapy in a dog model.

Methods

Pulp necrosis and periapical pathosis were induced in 40 mature double rooted premolars in four 2-year-old mongrel dogs. These teeth were randomly divided according to disinfection protocol into four equal groups (10 teeth each/20 roots), group I: DAP; group II: DL980 nm; group III: positive control (without treatment) and group IV: negative control (untouched teeth). These groups were further subdivided into 2 subgroups (5 teeth each/10 roots) according to evaluation period, subgroup (A): one month and subgroup (B): three months. Revascularization techniques were performed using bleeding induction and application of platelet rich fibrin (PRF). The coronal cavities were sealed with mineral trioxide aggregate (MTA) and glass ionomer cement. The inflammatory response, vital tissue in-growth, new hard tissue formation and bone resorption were assessed. Statistical analysis was done utilizing ANOVA, Tukey’s post hoc and paired t tests.

Results

In both subgroups, there were no significant differences between DAP and DL980 in terms of inflammatory cell count, vital tissue in-growth, new hard tissue formation and bone resorption (P ≤ 0.05).

Conclusion

Diode laser 980 nm can alternate DAP as a disinfection method of the root canal during RET for mature necrotic teeth, therefore it may accelerate regenerative endodontic therapy for both the patient and dentist and allows for RET in a single appointment.
Objective structured assessment ultrasound skill scale for hyomental distance competence – psychometric study
Authors: Gomes Sara Hora , Trindade Marta , Petrisor Cristina , Costa Dinis , Correia-Pinto Jorge , Costa Patrício S. , Pêgo José M.
Published: March 2023

Background

Ultrasound assessment of the airway recently integrates the point-of-care approach to patient evaluation since ultrasound measurements can predict a difficult laryngoscopy and tracheal intubation. Because ultrasonography is performer-dependent, a proper training and assessment tool is needed to increase diagnostic accuracy. An objective, structured assessment ultrasound skill (OSAUS) scale was recently developed to guide training and assess competence. This work aims to study the psychometric properties of OSAUS Scale when used to evaluate competence in ultrasound hyomental distance (HMD) measurement. Methods: Prospective and experimental study. Volunteers were recruited and enrolled in groups with different expertise. Each participant performed three ultrasonographic HMD evaluation. The performance was videorecorded and anonymized. Five assessors blindly rated participants’ performance using OSAUS scale and a Global Rating Scale (GRS). A psychometric study of OSAUS scale as assessment tool for ultrasound HMD competence was done. Results: Fifteen voluntaries participated on the study. Psychometric analysis of OSAUS showed strong internal consistency (Cronbach’s alpha 0.916) and inter-rater reliability (ICC 0.720; p < 0.001). The novice group scored 15.4±0.18 (mean±SD), the intermediate 14.3±0.75 and expert 13.6±0.1.25, with a significant difference between novice and expert groups (p = 0.036). The time in seconds to complete the task was evaluated: novice (90±34) (mean±SD), intermediate (84±23) and experts (83±15), with no significant differences between groups. A strong correlation was observed between OSAUS and global rating scale (r = 0.970, p < 0.001).

Conclusion

The study demonstrated evidence of validity and reliability. Further studies are needed to implement OSAUS scale in the clinical setting for training and assessment of airway ultrasound competence.
Isolation and characterisation of novel Methanocorpusculum species indicates the genus is ancestrally host-associated
Authors: Volmer James G. , Soo Rochelle M. , Evans Paul N. , Hoedt Emily C. , Astorga Alsina Ana L. , Woodcroft Benjamin J. , Tyson Gene W. , Hugenholtz Philip , Morrison Mark
Published: March 2023

Background

With an increasing interest in the manipulation of methane produced from livestock cultivation, the microbiome of Australian marsupials provides a unique ecological and evolutionary comparison with ‘low-methane’ emitters. Previously, marsupial species were shown to be enriched for novel lineages ofMethanocorpusculum, as well asMethanobrevibacter,Methanosphaera, andMethanomassiliicoccales. Despite sporadic reports ofMethanocorpusculumfrom stool samples of various animal species, there remains little information on the impacts of these methanogens on their hosts.

Results

Here, we characterise novel host-associated species ofMethanocorpusculum, to explore unique host-specific genetic factors and their associated metabolic potential. We performed comparative analyses on 176Methanocorpusculumgenomes comprising 130 metagenome-assembled genomes (MAGs) recovered from 20 public animal metagenome datasets and 35 other publicly availableMethanocorpusculumMAGs and isolate genomes of host-associated and environmental origin. Nine MAGs were also produced from faecal metagenomes of the common wombat (Vombatus ursinus) and mahogany glider (Petaurus gracilis), along with the cultivation of one axenic isolate from each respective animal;M. vombati(sp. nov.) andM. petauri(sp. nov.).

Conclusions

Through our analyses, we substantially expand the available genetic information for this genus by describing the phenotypic and genetic characteristics of 23 host-associated species ofMethanocorpusculum. These lineages display differential enrichment of genes associated with methanogenesis, amino acid biosynthesis, transport system proteins, phosphonate metabolism, and carbohydrate-active enzymes. These results provide insights into the differential genetic and functional adaptations of these novel host-associated species ofMethanocorpusculumand suggest that this genus is ancestrally host-associated.
Potential health and economic impact of paediatric vaccination using next-generation influenza vaccines in Kenya: a modelling study
Authors: Waterlow Naomi R. , Radhakrishnan Sreejith , Dawa Jeanette , van Leeuwen Edwin , Procter Simon R. , Lambach Philipp , Bresee Joseph , Mazur Marie , Eggo Rosalind M. , Jit Mark
Published: March 2023

Background

Influenza is a major year-round cause of respiratory illness in Kenya, particularly in children under 5. Current influenza vaccines result in short-term, strain-specific immunity and were found in a previous study not to be cost-effective in Kenya. However, next-generation vaccines are in development that may have a greater impact and cost-effectiveness profile.

Methods

We expanded a model previously used to evaluate the cost-effectiveness of seasonal influenza vaccines in Kenya to include next-generation vaccines by allowing for enhanced vaccine characteristics and multi-annual immunity. We specifically examined vaccinating children under 5 years of age with improved vaccines, evaluating vaccines with combinations of increased vaccine effectiveness, cross-protection between strains (breadth) and duration of immunity. We evaluated cost-effectiveness using incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits (INMBs) for a range of values for the willingness-to-pay (WTP) per DALY averted. Finally, we estimated threshold per-dose vaccine prices at which vaccination becomes cost-effective.

Results

Next-generation vaccines can be cost-effective, dependent on the vaccine characteristics and assumed WTP thresholds. Universal vaccines (assumed to provide long-term and broad immunity) are most cost-effective in Kenya across three of four WTP thresholds evaluated, with the lowest median value of ICER per DALY averted ($263, 95% Credible Interval (CrI): $ − 1698, $1061) and the highest median INMBs. At a WTP of $623, universal vaccines are cost-effective at or below a median price of $5.16 per dose (95% CrI: $0.94, $18.57). We also show that the assumed mechanism underlying infection-derived immunity strongly impacts vaccine outcomes.

Conclusions

This evaluation provides evidence for country-level decision makers about future next-generation vaccine introduction, as well as global research funders about the potential market for these vaccines. Next-generation vaccines may offer a cost-effective intervention to reduce influenza burden in low-income countries with year-round seasonality like Kenya.
GlyPerA™ effectively shields airway epithelia from SARS-CoV-2 infection and inflammatory events
Authors: Zaderer Viktoria , Dichtl Stefanie , Posch Wilfried , Abiatari Ivane , Bonn Günther K. , Jakschitz Thomas , Huber Lukas A. , Kurzchalia Teymuras V. , Wilflingseder Doris
Published: March 2023

New SARS-CoV-2 variants of concern (VOCs) and waning immunity illustrate that quick and easy-to-use agents are needed to prevent infection. To protect from viral transmission and subsequent inflammatory reactions, we applied GlyperA™, a novel antimicrobial formulation that can be used as mouth gargling solution or as nasal spray, to highly differentiated human airway epithelia prior infection with Omicron VOCs BA.1 and BA.2. This formulation fully protected polarized human epithelium cultured in air–liquid interphase (ALI) from SARS-CoV-2-mediated tissue destruction and infection upon single application up to two days post infection. Moreover, inflammatory reactions induced by the Omicron VOCs were significantly lowered in tissue equivalents either pre-treated with the GlyperA™ solution, or even when added simultaneously. Thus, the GlyperA™ formulation significantly shielded epithelial integrity, successfully blocked infection with Omicron and release of viral particles, and decreased intracellular complement C3 activation within human airway epithelial cell cultures. Crucially, our in vitro data imply that GlyperA™ may be a simple tool to prevent from SARS-CoV-2 infection independent on the circulating variant via both, mouth and nose.
Multi-modal body part segmentation of infants using deep learning
Authors: Voss Florian , Brechmann Noah , Lyra Simon , Rixen Jöran , Leonhardt Steffen , Hoog Antink Christoph
Published: March 2023

Background

Monitoring the body temperature of premature infants is vital, as it allows optimal temperature control and may provide early warning signs for severe diseases such as sepsis. Thermography may be a non-contact and wireless alternative to state-of-the-art, cable-based methods. For monitoring use in clinical practice, automatic segmentation of the different body regions is necessary due to the movement of the infant.

Methods

This work presents and evaluates algorithms for automatic segmentation of infant body parts using deep learning methods. Based on a U-Net architecture, three neural networks were developed and compared. While the first two only used one imaging modality (visible light or thermography), the third applied a feature fusion of both. For training and evaluation, a dataset containing 600 visible light and 600 thermography images from 20 recordings of infants was created and manually labeled. In addition, we used transfer learning on publicly available datasets of adults in combination with data augmentation to improve the segmentation results.

Results

Individual optimization of the three deep learning models revealed that transfer learning and data augmentation improved segmentation regardless of the imaging modality. The fusion model achieved the best results during the final evaluation with a mean Intersection-over-Union (mIoU) of 0.85, closely followed by the RGB model. Only the thermography model achieved a lower accuracy (mIoU of 0.75). The results of the individual classes showed that all body parts were well-segmented, only the accuracy on the torso is inferior since the models struggle when only small areas of the skin are visible.

Conclusion

The presented multi-modal neural networks represent a new approach to the problem of infant body segmentation with limited available data. Robust results were obtained by applying feature fusion, cross-modality transfer learning and classical augmentation strategies.
An indirect comparison of 144-week efficacy, safety, and tolerability of dolutegravir plus lamivudine and second-generation integrase inhibitor–based, 3-drug, single-tablet regimens in therapy-naive people with HIV-1
Authors: Evitt Lee A. , Nanji Sakina , Grove Richard A. , Okoli Chinyere , van Wyk Jean , Snedecor Sonya J.
Published: March 2023

Background

The long-term efficacy and safety of the 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) and 3-drug single-tablet regimens recommended for antiretroviral therapy (ART)-naive people with HIV-1 (PWH) have yet to be compared directly in clinical trials. This indirect treatment comparison (ITC) was conducted to compare the durability of efficacy and long-term safety of DTG + 3TC vs second-generation, integrase strand transfer inhibitor (INSTI)-based, 3-drug, single-tablet regimens bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and DTG/abacavir/3TC (DTG/ABC/3TC) at Week 144 after treatment initiation.

Methods

A systematic literature review identified 4 trials evaluating the treatment regimens of interest in ART-naive PWH (GEMINI-1, GEMINI-2, GS-US-380-1489, and GS-US-380-1490). Safety, efficacy, and tolerability results were compared using fixed-effects Bucher ITC methodology to calculate relative outcomes.

Results

Rates of virologic suppression (HIV-1 RNA < 50 copies/mL, US Food and Drug Administration Snapshot analysis) and virologic failure (HIV-1 RNA ≥ 50 copies/mL) as well as mean change in CD4 + cell count were similar with DTG + 3TC, BIC/FTC/TAF, and DTG/ABC/3TC at Week 144. Serious adverse events occurred less frequently with DTG + 3TC compared with both BIC/FTC/TAF (odds ratio [OR], 0.51; 95% CI 0.29–0.87; P = 0.014) and DTG/ABC/3TC (OR, 0.38; 95% CI 0.19–0.75; P = 0.006). Discontinuations and overall adverse events were similar across all 3 regimens.

Conclusions

These results suggest that the 2-drug regimen DTG + 3TC offers comparable and durable efficacy with fewer serious adverse events vs BIC/FTC/TAF and DTG/ABC/3TC through 144 weeks of treatment in ART-naive PWH. These long-term comparative data support the therapeutic value of DTG + 3TC for PWH.
Mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension
Authors: Kong Lei , Xie Yong-Sheng , Ma Xu-Dong , Huang Yan , Shang Xi-Fu
Published: March 2023

Background

This study aimed to investigate the potential mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension (ICMT).

Methods

According to the Pfirrmann grade evaluation classification, 30 human endplate cartilage tissues were divided into the lumbar vertebra fracture (LVF) group and lumbar disc herniation (LDH) group. Then, quantitative reverse transcription polymerase chain reaction, western blot, flow cytometry, hematoxylin–eosin staining, and senescence-associated β-galactosidase staining were performed. The difference in extracellular matrix expression between LVF and LDH endplate cartilage was detected. Second, the effect of ICMT on endplate chondrocytes degeneration was observed. Finally, the key regulatory role of YAP1 in ICMT-induced endplate cartilage degeneration was further verified.

Results

In degraded human endplate cartilage and tension-induced degraded endplate chondrocytes, the expression of YAP1, COL-2A, and Sox9 was decreased. Conversely, the expression of p53 and p21 was increased. By regulating YAP1 in vivo and in vitro, we can achieve alleviation of ICMT-induced senescence of endplate chondrocytes and effective treatment of disc degeneration.

Conclusions

ICMT could induce senescence and degeneration of endplate chondrocytes, and ICMT-induced senescence and degeneration of endplate chondrocytes could be alleviated by regulating YAP1 expression.
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

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

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

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

Enterotoxigenic 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

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

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

Background

Anthracnose 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.

Results

Thein 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.

Conclusion

The 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

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.