bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative and postoperative nomograms for predicting early recurrence of hepatocellular carcinoma without macrovascular invasion after curative resection
Authors: Zhang Yanfang , Lei Xuezhong , Xu Liangliang , Lv Xiaoju , Xu Mingqing , Tang Hong
Published: June 2022

Background

Postoperative early recurrence (ER) is a major obstacle to long-term survival after curative liver resection (LR) in patients with hepatocellular carcinoma (HCC). This study aimed to establish preoperative and postoperative nomograms to predict ER in HCC without macrovascular invasion.

Methods

Patients who underwent curative LR for HCC between January 2012 and December 2016 were divided into training and internal prospective validation cohorts. Nomograms were constructed based on independent risk factors derived from the multivariate logistic regression analyses in the training cohort. The predictive performances of the nomograms were validated using the internal prospective validation cohort.

Results

In total, 698 patients fulfilled the eligibility criteria. Among them, 265 of 482 patients (55.0%) in the training cohort and 120 of 216 (55.6%) patients in the validation cohort developed ER. The preoperative risk factors associated with ER were age, alpha-fetoprotein, tumor diameter, and tumor number, and the postoperative risk factors associated with ER were age, tumor diameter, tumor number, microvascular invasion, and differentiation. The pre- and postoperative nomograms based on these factors showed good accuracy, with concordance indices of 0.712 and 0.850 in the training cohort, respectively, and 0.754 and 0.857 in the validation cohort, respectively. The calibration curves showed optimal agreement between the predictions by the nomograms and actual observations. The area under the receiver operating characteristic curves of the pre- and postoperative nomograms were 0.721 and 0.848 in the training cohort, respectively, and 0.754 and 0.844 in the validation cohort, respectively.

Conclusions

The nomograms constructed in this study showed good performance in predicting ER for HCC without macrovascular invasion before and after surgery. These nomograms would be helpful for doctors when determining treatments and selecting patients for regular surveillance or administration of adjuvant therapies.
Analysing root roughness and smear layer relationship by comparing contemporary dental curettes with conventional dental curettes: a randomised controlled trial
Authors: Riaz Sania , Ahmed Shahbaz , Shabbir Sumaiya , Khan Ziaur Rahman , Zaidi Syed Jaffar Abbas , Naeem Meshal Muhammad , Farooqui Waqas Ahmed
Published: June 2022

Background

Root debridement procedures for the treatment of periodontal diseases, produces root surface irregularities and smear layer on the root surface that can adversely affect the healing of periodontal tissues. The objective of the present study was to evaluate the surface texture of root after hand instrumentation with Gracey curette, After Five curette, and Mini Five curette.

Methods

A randomised, controlled clinical trial was conducted with 120 participants clinically diagnosed with chronic periodontitis. Participants were equally randomised into four groups, with parallel treatment assignment of scaling and root planning using Gracey Curettes, After five and Mini five curette, and a control group with no instrumentation. Mobile teeth of these patients were then extracted atraumatically and analysed under a Scanning Electron Microscope and graded for "Roughness and Loss of Tooth substance index" and "Smear layer index." Cross Tabulation was made between the test groups (Control, Gracey Curette, After five, and Mini Five) versus "Roughness and Loss of Tooth substance Index" and "Smear Layer Index." A Chi-square test with Bonferroni correction was used to determine the graded distribution among the groups.

Results

In the control group, 73.3% of the teeth showed grade 1 roughness. In the Gracey group, 56.7% showed grade 2 roughness; in the After 5 group, 70% showed grade 3 roughness; in the Mini 5 group, 76.7% showed grade 3 roughness. A significant association was found between roughness scores and the use of individual instruments. Regarding smear layer formation, 46.7% of teeth showed a grade 4 smear layer in the control group. 50% of teeth showed grade 2 smear layer thickness in the Gracey group. In the After 5 group, 73.3% of teeth showed a grade 1 smear layer, while in the Mini 5 group, 80.0% showed a grade 1 smear layer. The use of individual instruments was significantly associated with the smear layer scores.

Conclusion

Gracey curettes produced relatively smoother root surfaces with less smear layer formation than After Five and Mini Five curettes, which produced relatively more roughened root surfaces with thicker smear layer formation.

Trial registration

ID: ClinicalTrials.gov Identifier: NCT04216966 Date of Registration: January 3, 2020.
Barriers and facilitators to attending and being physically active during recreation time among women incarcerated
Authors: Camplain Ricky , Williamson Heather J. , Pinn Travis A. , Shuman Sara , Robinson Bethany M. , Evans Maribeth , Luna Crystal
Published: June 2022

Background

Most women incarcerated in jail are not physically active and do not attend recreation time (rec-time), a time dedicated to being physically active, outside. The purpose of this study was to determine barriers and facilitators to attending and being physically active during rec-time among women incarcerated in jail.

Methods

We recruited and distributed a cross-sectional questionnaire to 100 women incarcerated at the Coconino County Detention Facility (CCDF) in Flagstaff, Arizona from March to July 2020. Women were asked about their experience with rec-time at CCDF, including if they had ever attended, how often they attended, if they exercised at rec-time, activities they participated in, and facilitators, barriers, and benefits to attend rec-time.

Results

Among 99 women who completed the questionnaire, 89% had ever attended rec-time. Most women identified environmental- and health-related facilitators to attending rec-time including enjoying natural light (74%), getting fresh air (83%), a change in environment (62%), and to move around and exercise (72%). Many women indicated environmental-, equipment-, clothing, and motivation-related barriers to attending rec-time. Specifically, women believed there was a lack of equipment (56%) and limited access to proper footwear (49%).

Conclusions

As health and environment are important facilitators and barriers to being physically active among women incarcerated in jail, it is important to identify appropriate environmental and policy interventions to increase the use of rec-time and physical activity. If a correctional facility does not offer rec-time or a similar alternative, one should be established, accessible, and welcoming.
Investigating pharmacy students’ therapeutic decision-making with respect to antimicrobial stewardship cases
Authors: Nasr Ziad G. , Alhaj Moustafa Diala , Dahmani Sara , Wilby Kyle J.
Published: June 2022

Background

Antimicrobial stewardship programs (ASPs) play a big role in minimizing antimicrobial resistance. Pharmacists are essential members of the health care team and in order for them to fulfill roles on ASP teams and become antimicrobial stewards, they must be prepared adequately by pharmacy schools prior to entry into actual practice. Although programming has been implemented into entry-to-practice programs worldwide, little is known about how students interpret antimicrobial stewardship (AMS) data and arrive at clinical decisions. We aimed to explore students’ cognitive processes and determine how they formulate therapeutic decisions when presented with AMS cases.

Methods

This was a qualitative study conducted using a case study approach, in which a sample (n=20) of pharmacy students was recruited to interpret AMS cases. Semi-structured 1-on-1 interviews were arranged with each participant. A think-aloud procedure with verbal protocol analysis was adopted to determine students’ decision-making processes. Thematic analysis was used to interpret themes from the interview data.

Results

Two themes were interpreted from the data: students’ focus and students’ approach to case interpretation. Students’ focus relates to external factors students consider when interpreting AMS case data and use to make and justify therapeutic decisions including patient-centered factors, drug-related factors, AMS interventions, and pharmacist’s role. Students’ clinical reasoning describes the approach that students use to interpret the data and the decision-making processes they employ to arrive at a clinical decision including a systematic approach versus non-systematic approach.

Conclusions

Students vary in their focus and the cognitive strategies used to interpret AMS cases. Findings support the notion that clinical reasoning and decision-making should be explicitly taught in pharmacy curricula, in order to help students become aware of their own cognitive processes and decision-making abilities.
The knowledge, barriers and opportunities to improve nutrition and physical activity amongst young people attending an Australian youth mental health service: a mixed-methods study
Authors: Mawer Tamieka , Kent Katherine , Williams Andrew D. , McGowan Courtney J. , Murray Sandra , Bird Marie-Louise , Hardcastle Sibella , Bridgman Heather
Published: June 2022

Background

Mental illnesses are the leading cause of disability in young people, and lifestyle interventions in young people at risk of mental illness remain a priority. Opportunities to improve nutrition and physical activity among young people through youth mental health services remain unclear. This study aimed to determine the knowledge and behaviors towards nutrition and physical activity, the barriers and enablers to improving behaviors, and the preferred providers and sources of information for nutrition and physical activity among a sample of young people attending a youth mental health service.

Methods

A mixed-method study was conducted in regional Tasmania, Australia in a sample of young people (15–25 years) attending a youth mental health service (headspace). A quantitative survey (n = 48) determined young people’s nutrition and physical activity knowledge, behaviors, barriers and enablers to achieving recommendations, and their preferred providers and sources of information. Structured interviews and a focus group further explored these concepts (n = 8), including the role of the mental health service as a provider of this support.

Results

The majority of participants did not meet national recommendations for nutrition and physical activity, despite possessing a high level of knowledge regarding their importance for mental health. Improving mental health was a common enabling factor for participants choosing to alter diet and physical activity habits, but also the leading barrier for participating in physical activity. Young people wanted to receive information from reputable health providers, ideally through social media sources. headspace was seen as an important potential provider of this information.

Conclusions

Our results indicate that there is a clear need to improve diet and physical activity habits to enhance mental and physical health outcomes in this at-risk group, and youth mental health services could provide further interventions to support their clients. Specialized staff (e.g. dietitians and exercise physiologists) may provide additional benefits alongside existing mental health care support.
Novel homozygous variant in the PDZD7 gene in a family with nonsyndromic sensorineural hearing loss
Authors: Du Qiang , Sun Qin , Gu Xiaodong , Wang Jinchao , Li Weitao , Guo Luo , Li Huawei
Published: June 2022

Hearing loss is the most common sensory neural disorder in humans, and according to a WHO estimation, 5.5% (466 million) of people worldwide have disabling hearing loss. In this study, a Chinese family with prelingual sensorineural hearing loss was investigated. The affected individuals showed moderately severe hearing loss at all frequencies. Using target genome enrichment and high-throughput sequencing, the homozygous variant c.2372del; p.(Ser791fs) was identified inPDZD7. This variant lies in exon 15 ofPDZD7and results in a frame shift followed by an early stop codon. It is classified as pathogenic according to the ACMG/AMP guidelines and ClinGen specifications. Our study expands the pathogenic variant spectrum ofPDZD7and strengthens the clinical importance of this gene in patients with moderately severe hearing loss.
Cellular and antibody response in GMZ2-vaccinated Gabonese volunteers in a controlled human malaria infection trial
Authors: Nouatin Odilon , Ibáñez Javier , Fendel Rolf , Ngoa Ulysse A. , Lorenz Freia-Raphaella , Dejon-Agobé Jean-Claude , Edoa Jean Ronald , Flügge Judith , Brückner Sina , Esen Meral , Theisen Michael , Hoffman Stephen L. , Moutairou Kabirou , Luty Adrian J. F. , Lell Bertrand , Kremsner Peter G. , Adegnika Ayola A. , Mordmüller Benjamin
Published: June 2022

Background

Antibody and cellular memory responses following vaccination are important measures of immunogenicity. These immune markers were quantified in the framework of a vaccine trial investigating the malaria vaccine candidate GMZ2.

Methods

Fifty Gabonese adults were vaccinated with two formulations (aluminum Alhydrogel and CAF01) of GMZ2 or a control vaccine (Verorab). Vaccine efficacy was assessed using controlled human malaria infection (CHMI) by direct venous inoculation of 3200 live Plasmodium falciparum sporozoites (PfSPZ Challenge). GMZ2-stimulated T and specific B-cell responses were estimated by flow cytometry before and after vaccination. Additionally, the antibody response against 212 P. falciparum antigens was estimated before CHMI by protein microarray.

Results

Frequencies of pro- and anti-inflammatory CD4+ T cells stimulated with the vaccine antigen GMZ2 as well as B cell profiles did not change after vaccination. IL-10-producing CD4+ T cells and CD20+ IgG+ B cells were increased post-vaccination regardless of the intervention, thus could not be specifically attributed to any malaria vaccine regimen. In contrast, GMZ2-specific antibody response increased after the vaccination, but was not correlated to protection. Antibody responses to several P. falciparum blood and liver stage antigens (MSP1, MSP4, MSP8, PfEMP1, STARP) as well as the breadth of the malaria-specific antibody response were significantly higher in protected study participants.

Conclusions

In lifelong malaria exposed adults, the main marker of protection against CHMI is a broad antibody pattern recognizing multiple stages of the plasmodial life cycle. Despite vaccination with GMZ2 using a novel formulation, expansion of the GMZ2-stimulated T cells or the GMZ2-specific B cell response was limited, and the vaccine response could not be identified as a marker of protection against malaria.

Trial registration PACTR; PACTR201503001038304; Registered 17 February 2015; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1038
The effectiveness of systemic antibiotics for osteomyelitis of the foot in adults with diabetes mellitus: a systematic review protocol
Authors: Uddin Akram , Russell David , Game Fran , Santos Derek , Siddle Heidi J.
Published: June 2022

Background

Osteomyelitis of the foot is a major complication of diabetes that can be limb and life threatening. Systemic antibiotic pharmacotherapy is often used first line to eradicate infection and allow restoration of devitalised bone.

The aim is to conduct a systematic review of the effectiveness of systemic antibiotics on osteomyelitis of the foot in adults with diabetes mellitus.

Methods

A systematic review of all interventional studies treating osteomyelitis with systemic antibiotics in participants with diabetes mellitus and an ulcer of the foot below the malleoli will be conducted. Studies not available in English and in people below the age of 18 will be excluded. Study selection will follow the Patient Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA‐P guidelines). The quality of the studies will be assessed using the Cochrane risk‐of‐bias tool (RoB 2) for all randomised controlled trials and the Newcastle–Ottawa Scale (NOS) will be used for non‐randomised controlled trials. Electronic databases will be searched with no timeline restrictions.

Data Extraction

All identified references will be imported to the Rayyan Application. Studies for eligibility will be screened by two reviewers. One reviewer will perform the data extraction and quality appraisal will be conducted by two authors. If sufficient data is available, the quality will be analysed and a meta‐analysis will be performed. Data synthesis will be conducted, and meta‐analysis undertaken using RevMan 5.4.1 Meta‐analysis software. Non‐parametric data may be compared between selective intervention and outcomes.

Discussion

The results of this systematic review will identify the effectiveness of systemic antibiotic therapy on osteomyelitis of the foot in people with diabetes based on the set outcome measure criteria. The findings will establish if there are existing consistent standards or variation in practice when treating diabetic foot osteomyelitis (DFO). The study may establish if guidelines are required to standardise practice when treating DFO with systemic antibiotic therapy. This systematic review protocol will synthesise the existing evidence on the effectiveness of systemic antibiotic therapy for treating DFO.

Trial registration

International Prospective Register for Systematic Reviews (PROSPERO) number CRD42021245424.
Role of different non-coding RNAs as ovarian cancer biomarkers
Authors: Beg Anam , Parveen Rafat , Fouad Hassan , Yahia M. E. , Hassanein Azza S.
Published: June 2022

Background

Among many gynecological malignancies ovarian cancer is the most prominent and leading cause of female mortality worldwide. Despite extensive research, the underlying cause of disease progression and pathology is still unknown. In the progression of ovarian cancer different non-coding RNAs have been recognized as important regulators. The biology of ovarian cancer which includes cancer initiation, progression, and dissemination is found to be regulated by different ncRNA. Clinically ncRNA shows high prognostic and diagnostic importance.

Results

In this review, we prioritize the role of different non-coding RNA and their perspective in diagnosis as potential biomarkers in the case of ovarian cancer. Summary of some of the few miRNAs involved in epithelial ovarian cancer their expression and clinical features are being provided in the table. Also, in cancer cell proliferation, apoptosis, invasion, and migration abnormal expression of piRNAs are emerging as a crucial regulator hence the role of few piRNAs is being given. Both tRFs and tiRNAs play important roles in tumorigenesis and are promising diagnostic biomarkers and therapeutic targets for cancer. lncRNA has shown a leading role in malignant transformation and potential therapeutic value in ovarian cancer therapy.

Conclusions

Hence in this review we demonstrated the role of different ncRNA that play an important role in serving strong potential as a therapeutic approach for the treatment of ovarian cancer.
Safety and efficacy of the Seraph® 100 Microbind® Affinity Blood Filter to remove bacteria from the blood stream: results of the first in human study
Authors: Eden Gabriele , Schmidt Julius J. , Büttner Stefan , Kümpers Philipp , Hafer Carsten , Rovas Alexandros , Koch Benjamin Florian , Schmidt Bernhard M. W. , Kielstein Jan T.
Published: June 2022

Background

Bacterial burden as well as duration of bacteremia influence the outcome of patients with bloodstream infections. Promptly decreasing bacterial load in the blood by using extracorporeal devices in addition to anti-infective therapy has recently been explored. Preclinical studies with the Seraph® 100 Microbind® Affinity Blood Filter (Seraph® 100), which consists of heparin that is covalently bound to polymer beads, have demonstrated an effective binding of bacteria and viruses. Pathogens adhere to the heparin coated polymer beads in the adsorber as they would normally do to heparan sulfate on cell surfaces. Using this biomimetic principle, the Seraph® 100 could help to decrease bacterial burden in vivo.

Methods

This first in human, prospective, multicenter, non-randomized interventional study included patients with blood culture positive bloodstream infection and the need for kidney replacement therapy as an adjunctive treatment for bloodstream infections. We performed a single four-hour hemoperfusion treatment with the Seraph® 100 in conjunction with a dialysis procedure. Post procedure follow up was 14 days.

Results

Fifteen hemodialysis patients (3F/12 M, age 74.0 [68.0–78.5] years, dialysis vintage 28.0 [11.0–45.0] months) were enrolled. Seraph® 100 treatment started 66.4 [45.7–80.6] hours after the initial positive blood culture was drawn. During the treatment with the Seraph® 100 with a median blood flow of 285 [225–300] ml/min no device or treatment related adverse events were reported. Blood pressure and heart rate remained stable while peripheral oxygen saturation improved during the treatment from 98.0 [92.5–98.0] to 99.0 [98.0–99.5] %; p = 0.0184. Four patients still had positive blood culture at the start of Seraph® 100 treatment. In one patient blood cultures turned negative during treatment. The time to positivity (TTP) was increased between inflow and outflow blood cultures by 36 [− 7.2 to 96.3] minutes. However, overall TTP increase was not statistical significant.

Conclusions

Seraph® 100 treatment was well tolerated. Adding Seraph® 100 to antibiotics early in the course of bacteremia might result in a faster resolution of bloodstream infections, which has to be evaluated in further studies.

Trail registration: ClinicalTrials.gov Identifier: NCT02914132, first posted September 26, 2016.
Livestock infected with Leishmania spp. in southern Iran
Authors: Rezaei Zahra , Pourabbas Bahman , Asaei Sadaf , Sepehrpour Shima , Ahmadnia Motlagh Sara , Pourabbas Parham , Abdolahi Khasibi Samaneh , Alborzi Abdolvahab
Published: June 2022

Background

The magnitude of the health problems caused by leishmaniasis has been a major driving factor behind the development and implementation of leishmaniasis control programs by the national authorities in Iran, with a priority for health and environmental management. Such programs are not achievable unless all of the factors leading to the infection, including the parasite’s life-cycle, vectors and reservoirs, are recognized. So far in Iran, humans and rodents have been considered the principal reservoirs of Leishmania tropica and Leishmania major, respectively, both associated with cutaneous leishmaniasis (CL), with domestic dogs considered to be the main reservoir for Leishmania infantum, associated with visceral leishmaniasis (VL). The role of other mammals in maintaining the Leishmania parasite has remained unclear. This study aimed to investigate Leishmania infection among livestock in endemic areas of VL and CL in Fars province, southern Iran, using serological and molecular methods.

Methods

Blood samples from 181 clinically healthy livestock, including 49 sheep, 114 goats, 16 cattle and two donkeys, were screened to detect Leishmania DNA and anti-Leishmania antibodies using qPCR (quantitative PCR) and the direct agglutination test (DAT), respectively. Four qPCR-positive samples were amplified using the internal transcribed spacer one (ITS1) primers in conventional PCR and sent for directional sequencing.

Results

Of the 181 livestock tested, 51 (28.2%) were infected with Leishmania, using serological and molecular methods. Anti-Leishmania antibodies were detected in 70 (38.7%) (95% confidence interval [CI]: 31.5–46.2) and Leishmania DNA in 93 (51.4%) (95% CI: 43.9–58.9) livestock. The identified Leishmania spp. were L. infantum and L. major.

Conclusions

The findings of the present study show a relatively high prevalence of Leishmania infection among livestock in endemic areas of the disease, in Fars province, southern Iran. Given the large population of this group of animals and the fact that they live in the vicinity of the main reservoirs of the disease and vectors, it seems that sand flies regularly bite these animals. Further studies are needed to determine the role of livestock in the parasite’s life-cycle and the epidemiology of Leishmania infection.

Graphical Abstract
Value of ultrasound fusion imaging in detecting vascular cerebral white matter pathology
Authors: Brunner Cornelia , Schreiber Stephan Joachim , Bokemeyer Martin , Ransmayr Gerhard , Struhal Walter , Olbert Elisabeth Daniela , Alhani Naela , Vosko Milan Rastislav
Published: June 2022

Background

Transcranial sonography is beside magnetic resonance imaging (MRI) and computed tomography, a well-established imaging method for evaluation of brain parenchyma and already implicated in various neurological disorders as bed-side investigation possibility in clinical routine. The aim of this study was the qualitative assessment detecting vascular white matter hyperintensities (WMHs), with ultrasound fusion-imaging technique (UFI) and to find the optimal location for their visualization in accordance to the grade of WMHs and to possibly providing a standardized protocol for clinical use.

Results

29 patients with WMHs of variable degree quantified according to Fazekas grading scale (n = 13 I; n = 9 II; n = 7 III) and 11 subjects with normal findings on MRI were identified for further analysis. Ultrasound images were analyzed to a standardized protocol and predefined anatomical landmarks. UFI could visualize the MRI-verified WMHs in 147 of 161 localizations (91%). The overall ultrasound detection rate of WMHs increased with higher degree of WMHs burden (I:85%, II:94%, III:97%). The highest sensitivity was achieved at the contralateral central part (CPc) (97%) of the lateral ventricle. The inter-rater analysis between 2 independent raters, who were blinded to the patient’s diagnosis and assessed only the B-mode ultrasound images, indicated an 86% agreement with an overall moderate strength of agreement (κ: 0.489, p < 0.0005) for all localizations. The highest accordance within raters was shown at the CPc; 92% (κ: 0.645, p < 0.0005).

Conclusions

This explorative study describes prospectively the ultrasound detection of periventricular vascular WMHs based on MRI lesions using UFI. Transcranial ultrasound (TCS) could serve as an additional screening opportunity for the detection of incidental WMLs during routine TCS investigations to initiate early vascular risk factor modification in primary prevention.
Is there an association between total physical activity level and VO2max among fitness club members? A cross-sectional study
Authors: Tangen Elene Mauseth , Gjestvang Christina , Stensrud Trine , Haakstad Lene A. H.
Published: June 2022

Background

Since cardiorespiratory fitness is an important predictor for all-cause mortality, it is of interest to know if meeting the physical activity (PA) recommendations is associated with higher levels of maximal oxygen uptake (VO2max). We aimed to investigate the association between total PA level given as counts per minute (cpm) and minutes in moderate-to-vigorous PA (MVPA), and VO2maxin new fitness club members.

Methods

A total of 62 men and 63 women (≥ 18 years), defined as healthy (no disease considered to hinder PA) participated in this study. VO2max(mL kg−1 min−1) was measured with a cardiopulmonary exercise (modified Balke protocol), and total PA level was measured with ActiGraph GT1M for seven consecutive days. All participants accumulating ≥ 10 h of activity recordings ≥ 4 days were included in the data analysis. To examine associations between PA level and VO2max, a Pearson correlation and a multiple linear regression analysis adjusted for covariates were used.

Results

VO2max(mL kg−1 min−1) was 40.5 ± 7.2 in men and 35.1 ± 6.0 in women. Total PA level (cpm) and MVPA (min) were 352.4 ± 123.4 and 260.0 ± 132.6 in men and 361.4 ± 103.8 and 273.2 ± 137.0 in women. Total PA level (men: r = 0.346,p < 0.01, women: r = 0.267p < 0.01) and MVPA (men: r = 0.359,p =  < 0.01, women: r = 0.236,p = 0.03) was associated with VO2max. When adjusting for age and body fat percentage, total PA level and MVPA were no longer associated with VO2max(men:p = 0.11 andp = 0.79, women:p = 0.40 andp = 0.61). In men, age (β = − 0.469p < 0.01) and body fat percentage (β = − 0.483,p < 0.01) were the strongest predictor for VO2max. For women, body fat percentage was the strongest predictor for VO2max(β = − 0.483,p < 0.01).

Conclusions

Total PA level and MVPA were associated with VO2max, but the association was low and diminished when adjusted for age and body fat percentage. Body fat percentage (men and women) and age (men) were more strongly associated with VO2maxthan total PA level and MVPA.
Mesenchymal stem cells improve redox homeostasis and mitochondrial respiration in fibroblast cell lines with pathogenic MT-ND3 and MT-ND6 variants
Authors: Navaratnarajah Tharsini , Bellmann Marlen , Seibt Annette , Anand Ruchika , Degistirici Özer , Meisel Roland , Mayatepek Ertan , Reichert Andreas , Baertling Fabian , Distelmaier Felix
Published: June 2022

The most frequent biochemical defect of inherited mitochondrial disease is isolated complex I deficiency. There is no cure for this disorder, and treatment is mainly supportive. In this study, we investigated the effects of human mesenchymal stem cells (MSCs) on skin fibroblast derived from three individuals with complex I deficiency carrying different pathogenic variants in mitochondrial DNA-encoded subunits (MT-ND3, MT-ND6). Complex I-deficient fibroblasts were transiently co-cultured with bone marrow-derived MSCs. Mitochondrial transfer was analysed by fluorescence labelling and validated by Sanger sequencing. Levels of reactive oxygen species (ROS) were measured using MitoSOX Red. Moreover, mitochondrial respiration was analysed by Seahorse XFe96 Extracellular Flux Analyzer. Levels of antioxidant proteins were investigated via immunoblotting. Co-culturing of complex I-deficient fibroblast with MSCs lowered cellular ROS levels. The effect on ROS production was more sustained compared to treatment of patient fibroblasts with culture medium derived from MSC cultures. Investigation of cellular antioxidant defence systems revealed an upregulation of SOD2 (superoxide dismutase 2, mitochondrial) and HO-1 (heme oxygenase 1) in patient-derived cell lines. This adaptive response was normalised upon MSC treatment. Moreover, Seahorse experiments revealed a significant improvement of mitochondrial respiration, indicating a mitigation of the oxidative phosphorylation defect. Experiments with repetitive MSC co-culture at two consecutive time points enhanced this effect. Our study indicates that MSC-based treatment approaches might constitute an interesting option for patients with mitochondrial DNA-encoded mitochondrial diseases. We suggest that this strategy may prove more promising for defects caused by mitochondrial DNA variants compared to nuclear-encoded defects.
Spotlight on therapeutic efficiency of mesenchymal stem cells in viral infections with a focus on COVID-19
Authors: Yasamineh Saman , Kalajahi Hesam Ghafouri , Yasamineh Pooneh , Gholizadeh Omid , Youshanlouei Hamed Rahmani , Matloub Saeed Karimi , Mozafari Masoud , Jokar Elham , Yazdani Yalda , Dadashpour Mehdi
Published: June 2022

The SARS-COV-2 virus has infected the world at a very high rate by causing COVID-19 disease. Nearly 507 million individuals have been infected with this virus, with approximately 1.2% of these patients being dead, indicating that this virus has been out of control in many countries. While researchers are investigating how to develop efficient drugs and vaccines versus the COVID-19 pandemic, new superseded treatments have the potential to reduce mortality. The recent application of mesenchymal stem cells (MSCs) in a subgroup of COVID-19 patients with acute respiratory distress has created potential benefits as supportive therapy for this viral contagion in patients with acute conditions and aged patients with severe pneumonia. Consequently, within this overview, we discuss the role and therapeutic potential of MSCs and the challenges ahead in using them to treat viral infections, with highlighting on COVID-19 infection.

Graphical Abstract
Sex-specific differences in zebrafish brains
Authors: Zhai Gang , Jia Jingyi , Bereketoglu Ceyhun , Yin Zhan , Pradhan Ajay
Published: June 2022

In this systematic review, we highlight the differences between the male and female zebrafish brains to understand their differentiation and their use in studying sex-specific neurological diseases. Male and female brains display subtle differences at the cellular level which may be important in driving sex-specific signaling. Sex differences in the brain have been observed in humans as well as in non-human species. However, the molecular mechanisms of brain sex differentiation remain unclear. The classical model of brain sex differentiation suggests that the steroid hormones derived from the gonads are the primary determinants in establishing male and female neural networks. Recent studies indicate that the developing brain shows sex-specific differences in gene expression prior to gonadal hormone action. Hence, genetic differences may also be responsible for differentiating the brain into male and female types. Understanding the signaling mechanisms involved in brain sex differentiation could help further elucidate the sex-specific incidences of certain neurological diseases. The zebrafish model could be appropriate for enhancing our understanding of brain sex differentiation and the signaling involved in neurological diseases. Zebrafish brains show sex-specific differences at the hormonal level, and recent advances in RNA sequencing have highlighted critical sex-specific differences at the transcript level. The differences are also evident at the cellular and metabolite levels, which could be important in organizing sex-specific neuronal signaling. Furthermore, in addition to having one ortholog for 70% of the human gene, zebrafish also shares brain structural similarities with other higher eukaryotes, including mammals. Hence, deciphering brain sex differentiation in zebrafish will help further enhance the diagnostic and pharmacological intervention of neurological diseases.
IL-1R/C3aR signaling regulates synaptic pruning in the prefrontal cortex of depression
Authors: Zhang Man-Man , Guo Min-Xia , Zhang Qiu-Ping , Chen Xue-Qin , Li Na-Zhi , Liu Qing , Cheng Jie , Wang Shi-Le , Xu Guang-Hui , Li Cheng-Fu , Zhu Ji-Xiao , Yi Li-Tao
Published: June 2022

Background

Major depressive disorder is characterized by not only monoamine neurotransmitters deficiencies but also persistent neuroinflammation. The complement system is an attractive therapeutic target for various inflammation-related diseases due to its early activation in inflammatory processes.

Results

In the present study, the dynamic alteration of complement C3 and its receptor C3aR during the occurrence of depression and the mechanism of astrocyte-microglia IL-1R/C3/C3aR on synaptic pruning were investigated. The proteomic analysis firstly showed that chronic stress caused an elevation of C3. GO analysis indicated that complement system-mediated synaptic pruning signaling was involved in depression. The dynamic observation indicated that C3/C3aR was activated in the early onset and throughout the course of depression induced by lipopolysaccharide (LPS) and chronic stress. In contrast, C3aR blockade inhibited the hyperactivation of microglial APT2/DHHC7 palmitoylation cycle, which mediated the translocation of STAT3 and the expression of proinflammatory cytokines. Meanwhile, C3aR blockade also attenuated the synaptic pruning and enhanced the synaptogenesis in the prefrontal cortex of mice. Moreover, the blockade of IL-1R/NF-κB signaling pathway reduced the release of C3 from astrocyte.

Conclusions

The current study demonstrates that astrocyte-microglia IL-1R/C3/C3aR activation causes the abnormal synaptic pruning in depression, and suggests that the activation of complement C3/C3aR may be particularly helpful in predicting the onset stage of depression.
Post-traumatic stress symptoms experienced by healthcare workers in Lebanon four months following Beirut’s ammonium nitrate explosion: a survey-based study
Authors: Bou Sanayeh Elie , El Chamieh Carolla , Saade Marie Christelle , Maalouf Rami George , Bizri Maya
Published: June 2022

Background

On August 4, 2020, Lebanon faced one of the deadliest mass casualty explosions the world has witnessed during the twenty-first century. The human and emotional tolls were heavy on attending physicians, clinical fellows, residents, interns, medical students, and registered nurses, who were working in dramatic conditions, triaging, and treating thousands of blast-related casualties. We evaluated the risk of developing post-traumatic stress disorder symptoms (PTSS), among these healthcare workers (HCWs) from different Lebanese hospitals.

Methods

This is a multicentered, cross-sectional study that was conducted in December 2020, using an online questionnaire that evaluated the risk of developing PTSS based on the validated self-reported PTSD-Checklist for DSM-V (PCL-5). We also explored possible correlates with the participants’ socio-demographic characteristics, job profile, mental health, and blast-related events.

Results

Out of 519 participants, 44% were at high risk of developing PTSS following Beirut-blast. Nurses, attending physicians, fellows, and participants who are older in age, married, or working at specific hospitals, were at a higher risk. Those identified at higher risk of PTSS were surgeons, anesthesiologists, emergency medicine doctors, or radiologists; and they were more likely to be willing to migrate; having a prior history of psychiatric medication intake for PTSD treatment, a prior history of PTSD, or a personal history of seeking mental health service. At last, the latter two parameters as well as the number of examined injuries, severe home damage, and testing positive for the COVID-19 virus during the two weeks’ period that followed the blast were found to be predictors for the development of PTSS.

Conclusion

Lebanese in-hospital HCWs were found to be at a high risk of developing PTSS following the Beirut-Blast, thus we recommend public health authorities to provide adequate resources to avoid the emergence of mental illnesses among these rescuers.
Protease-producing lactic acid bacteria with antibacterial properties and their potential use in soybean meal fermentation
Authors: Ma Hao , Wang Lei , Yu Haojie , Wang Weiwei , Wu Guofang , Qin Guangyong , Tan Zhongfang , Wang Yanping , Pang Huili
Published: June 2022

Background

As an adequate plant protein raw material, soybean meal has attracted extensive attention because of its high protein content, abundant amino acids essential for animals, and many functional nutrients. Feed fermentation is a new way to improve nutrient absorption of animals by inoculating microorganisms, which can also play a probiotic role. In order to screen the lactic acid bacteria with remarkable protease-producing performance and excellent growth and fermentation characteristics, 1000 strains isolated from different materials were evaluated in this study. After primary and re-screening, 22 strains both with protein clear zone diameters larger than 15.00 mm (including the diameter of a hole puncher 10.00 mm) and protease activities greater than 20.00 U/mL were screened out for physiological and biochemical tests, as well as antimicrobial performance tests.

Results

Strains P (Pig) 15 and ZZUPF (Zhengzhou University Pig Fecal) 95, which have excellent physiological and biochemical characteristics, as well as good inhibition abilities for Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, and Micrococcus luteus, were selected and used as fermenting agents for 3- and 30-day (d) fermentation of soybean meal. The analysis of microorganisms, fermentation quality, and chemical composition during fermentation revealed that all lactic acid bacteria addition groups had lower harmful bacteria and pH value, as well as higher lactic acid bacteria content and lactic acid level compared with CK and protease-treated groups. These effects were even better especially after 30 days of fermentation.

Conclusions

This study indicated that the selected strains Lactiplantibacillus plantarum subsp. plantarum P15 and Enterococcus faecalis ZZUPF95 could be considered as potential probiotics for fermenting soybean meal for further research.

Graphical abstract
Post-PRRT scans: which scans to make and what to look for
Authors: Aalbersberg Else A. , de Vries–Huizing Daphne M. V. , Tesselaar Margot E. T. , Stokkel Marcel P. M. , Versleijen Michelle W. J.
Published: June 2022

Aim

The aim of this study was to evaluate the clinical utility of SPECT/CT (imaging of uptake in tumor lesions and additional findings) and the additional value of planar imaging in order to simplify clinical imaging protocols and decrease patients burden.

Materials and methods

One hundred consecutive patients with metastatic neuroendocrine tumor (NET) treated with PRRT were included. Post-therapy imaging was performed 24 h after each PRRT cycle by both whole-body planar imaging and abdominal- and thoracic SPECT/CT. All images were evaluated for (1) the presence of new lesions, (2) discordant lesions between the two acquisitions (planar or SPECT), (3) location of lesions on SPECT (abdominal, thoracic, or both), and (4) additional findings on non-contrast enhanced CT imaging.

Results

In total 368 PRRT cycles including post-therapy imaging were performed in 100 patients. 45 patients had abdominal disease only, whilst in 55 patients the disease was observed on both abdominal and thoracic SPECT. 16 patients had known bone lesions that were visible only on planar imaging as these were out of range of the SPECT/CT. During PRRT, one patient developed multiple new bone metastases after the second cycle of PRRT, which were visible on both planar and SPECT/CT images. In 11 patients additional findings were found on CT images, the most common and relevant being bowel obstruction, pleural effusion, and ascites. Patients who developed ascites during PRRT appeared to do extremely poor; a post-hoc analysis showed that overall survival was 13.2 months in patients that showed ascites during PRRT at any moment and 37.9 months in patients without ascites (p < 0.001).

Conclusion

From a clinical point of view, thoracoabdominal SPECT/CT imaging is the preferred method for post-PRRT imaging; planar imaging had no added value over SPECT/CT in this cohort. In patients with abdominal disease only on baseline imaging, SPECT/CT of the abdomen only might be sufficient for imaging during the PRRT course. All accompanying CT images should be reviewed for additional findings, especially ascites, which is suggested to be a poor prognostic factor in patients receiving PRRT.
A case of strongly suspected Lynch syndrome with colorectal neuroendocrine carcinoma
Authors: Kobayashi Naoya , Yoshida Hiroshi , Kawaguchi Shinya , Shiraso Satoru , Nemoto Noriko , Fujikawa Nanako , Haji Yoichi , Kono Emiko , Kokubo Shoji , Tsukuda Kazuhiko , Asano Shigeyuki , Shinya Fumiaki
Published: June 2022

Background

Neuroendocrine cell carcinomas (NEC) of the colon and rectum are uncommon, representing ~ 0.1% of all colorectal carcinomas. They are associated with a much worse prognosis compared to adenocarcinoma of the colon and rectum, as death occurs in approximately half of all patients within 1 year. Lynch syndrome (LS) is the most common cause of inherited colorectal cancer, accounting for 2–4% of newly diagnosed colorectal cancer cases. This case is extremely rare which was strongly suspected LS as the background, and NEC as the histological type of colorectal cancer.

Case presentation

The patient was a 44-year-old man presenting with vomiting as the main complaint. He had undergone ileocecal resection for cecal cancer at age 29. The diagnosis was obstructive descending colorectal cancer, and colonoscopy revealed tumors in the rectum and sigmoid colon in addition. Due to multiple occurrences of colorectal cancer and its prevalence in the patient’s family, LS was suspected. The operation which was a subtotal proctocolectomy was performed. Pathological analysis revealed complete curative resection and the descending colon cancer of the obstructed portion was at the most advanced pathological Stage IIIC in UICC TNM classification, and the tissue type was a NEC. The Ki-67 index was 70%. The results of the microsatellite instability (MSI) test showed high-frequency MSI. The BRAF V600E variant was negative. The immunoexpression of MLH1 was positive, MSH2 was negative, PMS2 was positive, and MSH6 was negative.

Conclusions

Extended surgery is recommended for incipient colorectal cancer in LS cases in order to reliably reduce the risk of developing metachronous colorectal cancer. The survival outcome of surgery alone on digestive tract NECs, even locoregional lesions that are completely resection, is extremely poor. It is currently unclear if digestive tract NECs develop more readily in patients with LS. The accumulation of additional cases is necessary.
Development and evaluation of a remote training strategy for the implementation of mental health evidence-based practices in rural schools: pilot study protocol
Authors: Eiraldi Ricardo , McCurdy Barry L. , Khanna Muniya S. , Goldstein Jessica , Comly Rachel , Francisco Jennifer , Rutherford Laura E. , Wilson Tara , Henson Kathryn , Farmer Thomas , Jawad Abbas F.
Published: June 2022

Background

An increasing number of schools in rural settings are implementing multi-tier positive behavioral interventions and supports (PBIS) to address school-climate problems. PBIS can be used to provide the framework for the implementation of evidence-based practices (EBPs) to address children’s mental health concerns. Given the large service disparities for children in rural areas, offering EBPs through PBIS can improve access and lead to better long-term outcomes. A key challenge is that school personnel need technical assistance in order to implement EBPs with fidelity and clinical effectiveness. Providing ongoing on-site support is not feasible or sustainable in the majority of rural schools, due to their remote physical location. For this reason, remote training technology has been recommended for providing technical assistance to behavioral health staff (BHS) in under-served rural communities.

Objectives

The purpose of this study is to use the user-centered design, guided by an iterative process (rapid prototyping), to develop and evaluate the appropriateness, feasibility, acceptability, usability, and preliminary student outcomes of two online training strategies for the implementation of EBPs at PBIS Tier 2.

Methods

The study will employ a pragmatic design comprised of a mixed-methods approach for the development of the training platform, and a hybrid type 2, pilot randomized controlled trial to examine the implementation and student outcomes of two training strategies: Remote Video vs. Remote Video plus Coaching.

Discussion

There is a clear need for well-designed remote training studies focused on training in non-traditional settings. Given the lack of well-trained mental health professionals in rural settings and the stark disparities in access to services, the development and pilot-testing of a remote training strategy for BHS in under-served rural schools could have a significant public health impact.

Ethics and dissemination

The project was reviewed and approved by the institutional review board. Results will be submitted to ClinicalTrials.gov and disseminated to community partners and participants, peer-reviewed journals, and academic conferences.

Trial registration

ClinicialTrials.gov, NCT05034198 and NCT05039164