bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractHearing 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

Abstract
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

AbstractBackgroundOsteomyelitis 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.MethodsA 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 ExtractionAll 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.DiscussionThe 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 registrationInternational 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundSince 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.MethodsA 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.ResultsVO2max(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).ConclusionsTotal 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

AbstractThe 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

AbstractThe 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

AbstractIn 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.