bluuebunny/crossref_metadata_2025 huggingface dataset:
Pregnancy during COVID-19: social contact patterns and vaccine coverage of pregnant women from CoMix in 19 European countries
Authors: Wong Kerry L. M. , Gimma Amy , Paixao Enny S. ,   CoMix Europe Working Group, Paolotti Daniela , Karch André , Jäger Veronika , Baruch Joaquin , Melillo Tanya , Hudeckova Henrieta , Rosinska Magdalena , Niedzwiedzka-Stadnik Marta , Fischer Krista , Vorobjov Sigrid , Sõnajalg Hanna , Althaus Christian , Low Nicola , Reichmuth Martina , Auranen Kari , Nurhonen Markku , Petrović Goranka , Makaric Zvjezdana Lovric , Namorado Sónia , Caetano Constantino , Santos Ana João , Röst Gergely , Oroszi Beatrix , Karsai Márton , Fafangel Mario , Klepac Petra , Kranjec Natalija , Vilaplana Cristina , Casabona Jordi , Faes Christel , Beutels Philippe , Hens Niel , Jarvis Christopher I. , Edmunds W. John
Published: October 2022

Background

Evidence and advice for pregnant women evolved during the COVID-19 pandemic. We studied social contact behaviour and vaccine uptake in pregnant women between March 2020 and September 2021 in 19 European countries.

Methods

In each country, repeated online survey data were collected from a panel of nationally-representative participants. We calculated the adjusted mean number of contacts reported with an individual-level generalized additive mixed model, modelled using the negative binomial distribution and a log link function. Mean proportion of people in isolation or quarantine, and vaccination coverage by pregnancy status and gender were calculated using a clustered bootstrap.

Findings

We recorded 4,129 observations from 1,041 pregnant women, and 115,359 observations from 29,860 non-pregnant individuals aged 18–49. Pregnant women made slightly fewer contacts (3.6, 95%CI = 3.5–3.7) than non-pregnant women (4.0, 95%CI = 3.9–4.0), driven by fewer work contacts but marginally more contacts in non-essential social settings. Approximately 15–20% pregnant and 5% of non-pregnant individuals reported to be in isolation and quarantine for large parts of the study period.

COVID-19 vaccine coverage was higher in pregnant women than in non-pregnant women between January and April 2021. Since May 2021, vaccination in non-pregnant women began to increase and surpassed that in pregnant women.

Interpretation

Limited social contact to avoid pathogen exposure during the COVID-19 pandemic has been a challenge to many, especially women going through pregnancy. More recognition of maternal social support desire is needed in the ongoing pandemic. As COVID-19 vaccination continues to remain an important pillar of outbreak response, strategies to promote correct information can provide reassurance and facilitate informed pregnancy vaccine decisions in this vulnerable group.
Local recurrence as extraocular muscle lymphoma after 6 years of chronic myositis: a case report
Authors: Guo Qihan , Liu Rui , Zhang Xuan , Yang Bentao , Ma Jianmin
Published: October 2022

Background

Extraocular muscle is usually affected by thyroid disease or inflammatory pseudotumor, but seldom by neoplastic process. Primary malignant lymphoma involving isolated extraocular muscle is very rare, especially after 6 years of chronic myositis.

Case presentation

A middle-aged female presented with swelling of the lower lid of the right eye for 2 months. Magnetic resonance imaging showed significant enlargement of the right inferior rectus muscle belly. The patient first presented 6 years prior with upper eyelid swelling. A total of 5 surgical biopsies of the right eye were performed during 6 years with the following successive findings: inflammatory pseudotumor, chronic inflammation, inflammatory lesions, IgG4-related ophthalmic disease, and lastly, extraocular muscle extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).

Conclusion

MALT lymphoma may have occurred as a result of chronic extraocular myositis. Malignancy should be considered in patients with recurrent painless extraocular muscle hypertrophy. Differential diagnosis can rule out thyroid-associated ophthalmopathy (TAO), whose symptoms are similar. Diagnosis confirmation by biopsy is warranted if necessary.
Early child stimulation, linear growth and neurodevelopment in low birth weight infants
Authors: Upadhyay Ravi Prakash , Taneja Sunita , Strand Tor A. , Sommerfelt Halvor , Hysing Mari , Mazumder Sarmila , Bhandari Nita , Martines Jose , Dua Tarun , Kariger Patricia , Bahl Rajiv
Published: October 2022

Background

Children with low birth weight (LBW) are at risk of linear growth faltering and developmental deficits. Evidence suggests that early child stimulation and care reflected as responsive caregiving and opportunities for learning can promote development. The current analysis aimed to measure the extent to which linear growth and early child stimulation modify each other’s association with neurodevelopmental outcomes among LBW infants.

Methods

This is a secondary data analyses from a randomized controlled trial on the effect of community-initiated kangaroo mother care in LBW infants on their neurodevelopment at 12 months of corrected age. Bayley Scales of Infant and Toddler Development was used to assess cognitive, motor and language scores. Stimulation at home was assessed by the Pediatric Review of Children’s Environmental Support and Stimulation (PROCESS) tool. PROCESS scores were categorized into three groups: < Mean-1SD (low stimulation); Mean ± 1 SD (moderate stimulation)and > mean + 1SD (high stimulation).

Results

A total of 516 infants were available for neurodevelopment assessments. Interactions were observed between length for age z-score (LAZ) and PROCESS score categories. In the low stimulation group, the adjusted regression coefficients for the association between LAZ and cognitive, motor and language scores were substantially higher than in the moderate and high stimulation group. Stimulation was positively associated with neurodevelopmental outcomes in both stunted and non-stunted infants; however, the association was twice as strong in stunted than in non-stunted.

Conclusion

Moderate to high quality stimulation may alleviate the risk of sub-optimal development in LBW infants with linear growth deficits.

Clinical trial registration

The primary trial whose data are analysed is registered at clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT02631343).
Pediatric reference values of anterior visual pathway structures measured with axis-correction on high-resolution 3D T2 fast spin echo sequences
Authors: Markart Stefan , Wildermuth Simon , Geiss Johannes , Willems Erik P. , Sturm Veit , Ditchfield Michael , Waelti Stephan
Published: October 2022

Background

The size of the anterior visual pathway (AVP) structures is affected by patient age and pathology. Normative data is useful when determining whether pathology is present. AVP structures do not respect the standard planes of magnetic resonance (MR) imaging. The aim of this study was to produce normative age-related and axis-corrected data of the AVP structures using multiplanar reformation (MPR) of high-resolution 3D T2-weighted fast spin echo (3D T2w FSE) images.

Methods

For each patient 32 measurements of AVP structures were obtained in 145 children (2 months - 18 years) with normal brain MR studies on high-resolution 3D T2w FSE images adjusted to the axis of each AVP structure. Descriptive statistics were calculated for different age classes and growth models were fitted to the data and assessed for their performance to create a formal statistical model that allows inference beyond the sample.

Results

Descriptive statistics were compiled in a reference table and prediction plots in relation to age, height, and body surface area (BSA) were obtained from the best overall performing statistical model, also taking field strength (1.5 vs. 3 T) into account. Intraclass correlation coefficient values were calculated for all variables ranging from 0.474 to 0.967, the most reliable being the transverse diameter of the globe, the maximum diameter of the retrobulbar nerve sheath, the intracranial segment of the optic nerve and the transverse diameter of the chiasm. The maximum retrobulbar diameter of the optic nerve sheath and the lateral superoinferior diameter of the chiasm showed no statistically significant change with age.

Conclusion

Detailed charts of reference values for AVP structures as well as prediction plots in relation to age, height and BSA were established using axis-corrected measurements from the MPR of high-resolution 3D T2w FSE images. Furthermore, an Excel spreadsheet that allows users to calculate normative values for the 9 AVP structures of key interest is provided as supplementary material.
Treatment of benign bone lesions with an injectable biphasic bone substitute
Authors: Döring Kevin , Rentenberger Colleen , Kolb Alexander , Patsch Janina , Puchner Stephan , Windhager Reinhard , Chiari Catharina
Published: October 2022

Background

Injectable biphasic ceramic bone substitutes (BCBSs) represent a modern alternative to conventional options for bone defect filling, as they further open the possibilities for percutaneous cavity reconstruction. Although recent studies have shown good surgical outcomes after treatment with BCBSs, mid-term follow-up data are still missing.

Patients and methods

Between 2013 and 2017, 18 patients were [1] treated with BCBS [2] for benign bone lesions and [3] had a complete set of retrospective information, including surgical protocols, imaging, patient dismission letters and outpatient clinic protocols, [4] with a minimum follow-up time of one year. Eleven patients received percutaneous surgery, while 7 patients had open curettage and BCBS filling. The median follow-up time was 36.5 (range 12–80) months.

Results

Local recurrence was reported in four patients. A distinctive bone remodelling pattern was noted on follow-up X-ray and magnetic resonance imaging showing a double-line phenomenon and continuously increasing cortical thickness one year after treatment in nine of thirteen patients. Regarding surgical complications, one patient suffered from a septic complication that required BCBS removal and lavage. One patient experienced superficial surgical site inflammation with redness and swelling, while two other patients had prolonged wound secretion.

Conclusion

In a limited case series, the studied BCBS demonstrated acceptable surgical outcomes. Initial wound leakage and recurrence seemed to be associated with percutaneous injection. Further studies are needed to compare recurrence and bone graft resorption after open and percutaneous bone cyst surgeries and to further evaluate postoperative surgical site inflammation, which appears self-limiting in most cases.
Risk factors of transport gap bending deformity in the treatment of critical-size bone defect after bone transport
Authors: Abula Abulaiti , Cheng Erlin , Abulaiti Alimujiang , Liu Kai , Liu Yanshi , Ren Peng
Published: October 2022

Background

The purpose of this study was to investigate the risk factors of transport gap bending deformity (TGBD) in the treatment of critical-size bone defect (CSBD) after the removal of the external fixator.

Methods

From January 2008 to December 2019, 178 patients with bone defects of the lower extremity caused by infection were treated by bone transport using a unilateral external fixator in our medical institution. TGBD was defined as the bone callus in the distraction area with a deviation to the force line of the femur (> 10°) or tibia (> 12°) after removal of the external fixator. The Association for the Study and Application of the Method of Ilizarov (ASAMI) standard was applied to assess the bone and functional outcomes. After the data were significant by the T-test or Pearson’s Chi-square test was analyzed, odds ratios were calculated using logistic regression tests to describe factors associated with the diagnosis of TGBD.

Results

A total of 178 patients were enrolled in the study, with a mean follow-up time of 28.6 ± 3.82 months. The positive result of the bacteria isolated test was observed in 144 cases (80.9%). The rate of excellent and good in the bone outcomes (excellent/good/fair/poor/failure, 41/108/15/14/0) was 83.7%, and 92.3% in the functional results (excellent/good/fair/poor/failure, 50/98/16/14/0) according to the ASAMI criteria. TGBD after removal of external fixator occurred in twenty-two patients (12.3%), including 6 tibias, and 16 femurs. Age > 45 years, BMI > 25 kg/m2, femoral defect, diabetes, osteoporosis, glucocorticoid intake, duration of infection > 24 months, EFT > 9 months, EFI > 1.8 month/cm were associated significantly with a higher incidence of TGBD in the binary logistic regression analysis (P < 0.05). The incidence more than 50% was found in patients with femoral defect (76.1%), osteoporosis (72.7%), BMI > 25 kg/m2 (69.0%), diabetes (59.5%), glucocorticoid intake (54.7%). In the multivariate logistic regression analyses, the following factors were associated independently with TGBD, including age > 45 years, BMI > 25 kg/m2, femoral defect, diabetes, and osteoporosis.

Conclusions

Bone transport using a unilateral external fixator was a safe and practical method in the treatment of CSBD caused by infection. The top five risk factors of TGBD included femoral defect, BMI > 25 kg/m2, duration of bone infection > 24 months, age > 45 years, and diabetes. Age > 45 years, BMI > 25 kg/m2, femoral defect, osteoporosis, and diabetes were the independent risk factors. The higher incidence of TGBD may be associated with more risk factors.
Feasibility and effectiveness of self-monitoring of blood glucose among insulin-dependent patients with type 2 diabetes: open randomized control trial in three rural districts in Rwanda
Authors: Ng’ang’a Loise , Ngoga Gedeon , Dusabeyezu Symaque , Hedt-Gauthier Bethany L. , Harerimana Emmanuel , Niyonsenga Simon Pierre , Bavuma Charlotte M. , Bukhman Gene , Adler Alma J. , Kateera Fredrick , Park Paul H.
Published: October 2022

Background

The prevalence of type 2 diabetes in sub Saharan Africa (SSA) has been on the rise. Effective control of blood glucose is key towards reducing the risk of diabetes complications. Findings mainly from high-income countries have demonstrated the effectiveness of self-monitoring of blood-glucose (SMBG) in controlling blood glucose levels. However, there are limited studies describing the implementation of SMBG in rural SSA. This study explores the feasibility and effectiveness of implementing SMBG among patients diagnosed with insulin-dependent type 2 diabetes in rural Rwanda.

Methods

Participants were randomized into intervention (n = 42) and control (n = 38) groups. The intervention group received a glucose-meter, blood test-strips, log-book, waste management box and training on SMBG in addition to usual care. The control group continued with their usual care consisting of, routine monthly medical consultation and health education. The primary outcomes were adherence to the implementation of SMBG (testing schedule and recording data in the log-book) and change in hemoglobin A1c. Descriptive statistics and a paired t-test were used to analyze the primary outcomes.

Results

In both the intervention and control arms, majority of the participants were female (59.5% vs 52.6%) and married (71.4% vs 73.7%). Most had at most a primary level education (83.3% vs. 89.4%) and were farmers (54.8% vs. 50.0%). Among those in the intervention group, 63.4% showed good adherence to implementing SMBG based on the number of tests recorded in the glucose meter. Only 20.3% demonstrated accurate recording of the glucose level tests in log-books. The mean difference of the HbA1C from baseline to six months post-intervention was significantly better among the intervention group -0.94% (95% CI -1.46, -0.41) compared to the control group 0.73% (95% CI -0.09, 1.54) p < 0.001.

Conclusion

Our study showed that among patients with insulin-dependent type 2 diabetes residing in rural Rwanda, SMBG was feasible and demonstrated positive outcomes in improving blood glucose control. However, there is need for strategies to enhance accuracy in recording blood glucose test results in the log-book.

Trial registration

The trial was registered retrospectively on the Pan African Clinical Trial Registry, on 17th May 2019. The registration number is PACTR201905538846394.
Periosteum coverage versus collagen-membrane coverage in periodontally accelerated osteogenic orthodontics: a randomized controlled clinical trial in Class II and Class III malocclusions
Authors: Ma Zhigui , Zhu Yan , Zhan Yining , Zhang Yufan , Abdelrehem Ahmed , Wang Bian , Yang Chi
Published: October 2022

Background

Periodontal accelerated osteogenic orthodontics (PAOO) is a widely-used clinical procedure that combines selective alveolar corticotomy, particulate bone grafting, and the application of orthodontic forces. Different modifications of PAOO such as collagen-membrane coverage can better benefit patients from preventing displacement of grafts. Due to its stability, collagen-membrane coverage gradually gained popularity and became a widely-used procedure in traditional PAOO technique.

Objectives

To quantitatively investigate the radiographic changes of alveolar bone, periodontal soft tissue changes of the mandibular anterior teeth and postoperative complications in periosteum-covered techniques compared with traditional surgical technique in PAOO.

Methods

Orthodontic camouflage for dental Class II or decompensation for skeletal Class III malocclusions were included; Patients with bone defects on the buccal aspects of the anterior mandible regions confirmed by clinical and radiographic examination were randomly divided into the periosteum coverage group or traditional technique group for PAOO. Cone-beam computerized tomography (CBCT) scans were obtained before treatment (T0) and 1 week (T1) and 12 months (T2) after operation. The primary outcome variable was the vertical alveolar bone level (VBL), the secondary evaluation parameters included labial horizontal bone thickness at the midpoint of the middle third (MHBT) or apical third (AHBT) to the limit of the labial cortical surface during a 12-month follow-up. Postoperative sequelae were evaluated after 2 days and 7 days in both the groups. Periodontal parameters were analyzed at T0 and T2.

Results

Thirty-six adult subjects were eligible and recruited in the present study. Although experimental group exhibited more severe infection, no significant differences of the postoperative symptoms or periodontal parameters was found between the 2 groups (P > 0.05). All patients were examined respectively using CBCT at baseline (T0), postoperative 1 week (T1) and 12 months (T2). Both alveolar bone height and width increased from T0 to T1 (P < 0.001) and then reduced from T1 to T2 (P < 0.001) in both groups. However, significant bone augmentation was achieved in each group from T0 to T2 (P < 0.001). Furthermore, the vertical alveolar bone augmentation in the experimental group increased significantly than that in the traditional surgery (P < 0.05).

Conclusions

Compared with traditional PAOO surgery, the periosteum-covered technique provides superior graft stabilization and satisfactory vertical bone augmentation in the labial mandibular anterior area.
Evaluation of therapeutic effects of crocin in attenuating the progression of diabetic nephropathy: a preliminary randomized triple-blind placebo-controlled trial
Authors: Jaafarinia Asma , Kafami Behzad , Sahebnasagh Adeleh , Saghafi Fatemeh
Published: October 2022

Background

Diabetic nephropathy (DN) is one of the most important complications of type 2 diabetes (T2DM). Oxidative stress and inflammatory cytokines play an essential role in the development and progression of DN. Despite adopting appropriate therapies, many patients with DN progress to end-stage renal disease (ESRD). Therefore, exploring innovative strategies for better management of DN is crucial. Crocin, a natural compound found in saffron, has profound antioxidant, antifibrotic and anti-inflammatory properties. This study aimed to evaluate the therapeutic effects of crocin in attenuation of the progression of DN.

Methods

In this randomized, triple-blind, placebo-controlled clinical trial, 44 patients with T2DM and microalbuminuria were randomly assigned to receive either crocin (15 mg/day) or a placebo for 90 days. Eventually, 40 patients completed the study: 21 patients in the crocin group and 19 in the placebo group. The primary outcome was a change in urine Albumin-to-Creatinine Ratio (uACR) from baseline to the end of the treatment period. We also evaluated metabolic, anthropometric, and biochemical parameters as the secondary outcomes.

Results

The results of the present study showed that uACR increased in both groups, but the increment was not significantly higher in the crocin group compared with the placebo. Serum levels of transforming growth factor-β (TGF-β) decreased in the crocin group and increased in the placebo group, but none of these changes was significant. Crocin significantly reduced triglyceride (TG) as an important metabolic parameter (P-Value = 0.03).

Conclusion

This study has shown that crocin may be a safe and potential adjunct to conventional therapies for DN patients but because of our limitations such as short duration of the treatment period, and prescribing low doses of crocin, we could not achieve the significant level.
Near-peers effectively teach clinical documentation skills to early medical students
Authors: Kusnoor Anita Vijay , Balchandani Rajeev , Pillow Malford Tyson , Sherman Stephanie , Ismail Nadia
Published: October 2022

Background

Composing the History of Present Illness (HPI), a key component of medical communication, requires critical thinking. Small group learning strategies have demonstrated superior effectiveness at developing critical thinking skills. Finding sufficient faculty facilitators for small groups remains a major gap in implementing these sessions. We hypothesized that “near-peer” teachers could effectively teach HPI documentation skills and fill the gap of small group facilitators. Here, we present a head-to-head comparison of near-peer and faculty teaching outcomes.

Methods

Second-year medical students in a single institution participated in an HPI Workshop as a clinical skills course requirement. Students were randomly assigned a near-peer or faculty facilitator for the workshop. We compared mean facilitator evaluation scores and performance assessments of students assigned to either type of facilitator.

Results

Three hundred sixty-five students, 29 residents (near-peers) and 16 faculty participated. On post-session evaluations (5-point Likert scale), students ranked near-peer facilitators higher than faculty facilitators on encouraging participation and achieving the goals of the session (residents 4.9, faculty 4.8), demonstrating small, statistically significant differences between groups. Mean scores on written assessments after the workshop did not differ between the groups (29.3/30 for a written H&P and 9/10 for an HPI exam question).

Conclusions

Near-peer facilitators were as effective as faculty facilitators for the HPI Workshop. Utilizing near-peers to teach HPI documentation skills provided teaching experiences for residents and increased the pool of available facilitators.
Understanding how and under what circumstances decision coaching works for people making healthcare decisions: a realist review
Authors: Zhao Junqiang , Jull Janet , Finderup Jeanette , Smith Maureen , Kienlin Simone Maria , Rahn Anne Christin , Dunn Sandra , Aoki Yumi , Brown Leanne , Harvey Gillian , Stacey Dawn
Published: October 2022

Background

Decision coaching is non-directive support delivered by a trained healthcare provider to help people prepare to actively participate in making healthcare decisions. This study aimed to understand how and under what circumstances decision coaching works for people making healthcare decisions.

Methods

We followed the realist review methodology for this study. This study was built on a Cochrane systematic review of the effectiveness of decision coaching interventions for people facing healthcare decisions. It involved six iterative steps: (1) develop the initial program theory; (2) search for evidence; (3) select, appraise, and prioritize studies; (4) extract and organize data; (5) synthesize evidence; and (6) consult stakeholders and draw conclusions.

Results

We developed an initial program theory based on decision coaching theories and stakeholder feedback. Of the 2594 citations screened, we prioritized 27 papers for synthesis based on their relevance rating. To refine the program theory, we identified 12 context-mechanism-outcome (CMO) configurations. Essential mechanisms for decision coaching to be initiated include decision coaches’, patients’, and clinicians’ commitments to patients’ involvement in decision making and decision coaches’ knowledge and skills (four CMOs). CMOs during decision coaching are related to the patient (i.e., willing to confide, perceiving their decisional needs are recognized, acquiring knowledge, feeling supported), and the patient-decision coach interaction (i.e., exchanging information, sharing a common understanding of patient’s values) (five CMOs). After decision coaching, the patient’s progress in making or implementing a values-based preferred decision can be facilitated by the decision coach’s advocacy for the patient, and the patient’s deliberation upon options (two CMOs). Leadership support enables decision coaches to have access to essential resources to fulfill their role (one CMOs).

Discussion

In the refined program theory, decision coaching works when there is strong leadership support and commitment from decision coaches, clinicians, and patients. Decision coaches need to be capable in coaching, encourage patients’ participation, build a trusting relationship with patients, and act as a liaison between patients and clinicians to facilitate patients’ progress in making or implementing an informed values-based preferred option. More empirical studies, especially qualitative and process evaluation studies, are needed to further refine the program theory.
Toward efficient and high-fidelity metagenomic data from sub-nanogram DNA: evaluation of library preparation and decontamination methods
Authors: Wang Chun , Zhang Li , Jiang Xuan , Ma Wentai , Geng Hui , Wang Xue , Li Mingkun
Published: October 2022

Background

Shotgun metagenomic sequencing has greatly expanded the understanding of microbial communities in various biological niches. However, it is still challenging to efficiently convert sub-nanogram DNA to high-quality metagenomic libraries and obtain high-fidelity data, hindering the exploration of niches with low microbial biomass.

Results

To cope with this challenge comprehensively, we evaluated the performance of various library preparation methods on 0.5 pg–5 ng synthetic microbial community DNA, characterized contaminants, and further applied different in silico decontamination methods. First, we discovered that whole genome amplification prior to library construction led to worse outcomes than preparing libraries directly. Among different non-WGA-based library preparation methods, we found the endonuclease-based method being generally good for different amounts of template and the tagmentation-based method showing specific advantages with 0.5 pg template, based on evaluation metrics including fidelity, proportion of designated reads, and reproducibility. The load of contaminating DNA introduced by library preparation varied from 0.01 to 15.59 pg for different kits and accounted for 0.05 to 45.97% of total reads. A considerable fraction of the contaminating reads were mapped to human commensal and pathogenic microbes, thus potentially leading to erroneous conclusions in human microbiome studies. Furthermore, the best performing in silico decontamination method in our evaluation, Decontam-either, was capable of recovering the real microbial community from libraries where contaminants accounted for less than 10% of total reads, but not from libraries with heavy and highly varied contaminants.

Conclusions

This study demonstrates that high-quality metagenomic data can be obtained from samples with sub-nanogram microbial DNA by combining appropriate library preparation and in silico decontamination methods and provides a general reference for method selection for samples with varying microbial biomass.
Identification and functional analysis of variants of MYH6 gene promoter in isolated ventricular septal defects
Authors: Zuo Ji-Yang , Chen Huan-Xin , Liu Zhi-Gang , Yang Qin , He Guo-Wei
Published: October 2022

Background

Ventricular septal defect is the most common form of congenital heart diseases. MYH6 gene has a critical effect on the growth and development of the heart but the variants in the promoter of MYH6 is unknown.

Patients and methods

In 604 of the subjects (311 isolated and sporadic ventricular septal defect patients and 293 healthy controls), DNA was extracted from blood samples and MYH6 gene promoter region variants were analyzed by sequencing. Further functional verification was performed by cellular experiments using dual luciferase reporter gene analysis, electrophoretic mobility shift assays, and bioinformatics analysis.

Results

Nine variants were identified in the MYH6 gene promoter and two of those variants [g.4085G>C(rs1222539675) and g.4716G>A(rs377648095)] were only found in the ventricular septal defect patients. Cellular function experiments showed that these two variants reduced the transcriptional activity of the MYH6 gene promoter (p < 0.001). Further analysis with online JASPAR database suggests that these variants may alter a set of putative transcription factor binding sites that possibly lead to changes in myosin subunit expression and ventricular septal defect formation.

Conclusions

Our study for the first time identifies variants in the promoter region of the MYH6 gene in Chinese patients with isolated and sporadic ventricular septal defect. These variants significantly reduced MYH6 gene expression and affected transcription factor binding sites and therefore are pathogenic. The present study provides new insights in the role of the MYH6 gene promoter region to better understand the genetic basis of VSD formation.
Co-modulation of T cells and B cells enhances the inhibition of inflammation in experimental hypersensitivity pneumonitis
Authors: Courtemanche Olivier , Huppé Carole-Ann , Blais Lecours Pascale , Lerdu Ophélie , Roy Joanny , Lauzon-Joset Jean-François , Blanchet Marie-Renée , Morissette Mathieu C. , Marsolais David
Published: October 2022

Background

Hypersensitivity pneumonitis (HP) is an interstitial lung disease characterized by antigen-triggered neutrophilic exacerbations. Although CD4+T cells are sufficient for HP pathogenesis, this never translated into efficient T cell-specific therapies. Increasing evidence shows that B cells also play decisive roles in HP. Here, we aimed to further define the respective contributions of B and T cells in subacute experimental HP.

Methods

Mice were subjected to a protocol of subacute exposure to the archaeonMethanosphaera stadmanaeto induce experimental HP. Using models of adoptive transfers of B cells and T cells in Rag1-deficient mice and of B cell-specific S1P1deletion, we assessed the importance of B cells in the development of HP by evaluating inflammation in bronchoalveolar lavage fluid. We also aimed to determine if injected antibodies targeting B and/or T cells could alleviate HP exacerbations using a therapeutic course of intervention.

Results

Even though B cells are not sufficient to induce HP, they strongly potentiate CD4+T cell-induced HP‑associated neutrophilic inflammation in the airways. However, the reduction of 85% of lung B cells in mice with a CD19-driven S1P1deletion does not dampen HP inflammation, suggesting that lung B cells are not necessary in large numbers to sustain local inflammation. Finally, we found that injecting antibodies targeting B cells after experimental HP was induced does not dampen neutrophilic exacerbation. Yet, injection of antibodies directed against B cells and T cells yielded a potent 76% inhibition of neutrophilic accumulation in the lungs. This inhibition occurred despite partial, sometimes mild, depletion of B cells and T cells subsets.

Conclusions

Although B cells are required for maximal inflammation in subacute experimental HP, partial reduction of B cells fails to reduce HP-associated inflammation by itself. However, co-modulation of T cells and B cells yields enhanced inhibition of HP exacerbation caused by an antigenic rechallenge.
Optical genome mapping identifies clinically relevant genomic rearrangements in prostate cancer biopsy sample
Authors: Shim Yeeun , Lee Jongsoo , Seo Jieun , Park Cheol Keun , Shin Saeam , Han Hyunho , Lee Seung-Tae , Choi Jong Rak , Chung Byung Ha , Choi Young Deuk
Published: October 2022

Background

Prostate cancer (PCa) is characterized by complex genomic rearrangements such as the ETS oncogene family fusions, yet the clinical relevance is not well established. While paneled genetic tests of DNA repair genes are recommended in advanced PCa, conventional genomic or cytogenetic tools are not ideal for genome-wide screening of structural variations (SVs) such as balanced translocation due to cost and/or resolution issues.

Methods

In this study, we tested the feasibility of whole-genome optical genomic mapping (OGM), a newly developed platform for genome-wide SV analysis to detect complex genomic rearrangements in consecutive unselected PCa samples from MRI/US-fusion targeted biopsy.

Results

We tested ten samples, and nine (90%) passed quality check. Average mapping rate and coverage depth were 58.1 ± 23.7% and 157.3 ± 97.7×, respectively (mean ± SD). OGM detected copy number alterations such as chr6q13 loss and chr8q12-24 gain. Two adjacent tumor samples were distinguished by inter/intra-chromosomal translocations, revealing that they’re from the same ancestor. Furthermore, OGM detected large deletion of chr13q13.1 accompanied by inter-chromosomal translocation t(13;20)(q13.1;p13) occurring within BRCA2 gene, suggesting complete loss of function.

Conclusion

In conclusion, clinically relevant genomic SVs were successfully detected in PCa samples by OGM. We suggest that OGM can complement panel sequencing of DNA repair genes BRCA1/2 or ATM in high-risk PCa.
An overview on nanoparticle-based strategies to fight viral infections with a focus on COVID-19
Authors: Yasamineh Saman , Kalajahi Hesam Ghafouri , Yasamineh Pooneh , Yazdani Yalda , Gholizadeh Omid , Tabatabaie Raheleh , Afkhami Hamed , Davodabadi Fatemeh , farkhad Alireza Khanalipour , Pahlevan Daryoush , Firouzi-Amandi Akram , Nejati-Koshki Kazem , Dadashpour Mehdi
Published: October 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to COVID-19 and has become a pandemic worldwide with mortality of millions. Nanotechnology can be used to deliver antiviral medicines or other types of viral reproduction-inhibiting medications. At various steps of viral infection, nanotechnology could suggest practical solutions for usage in the fight against viral infection. Nanotechnology-based approaches can help in the fight against SARS-CoV-2 infection. Nanoparticles can play an essential role in progressing SARS-CoV-2 treatment and vaccine production in efficacy and safety. Nanocarriers have increased the speed of vaccine development and the efficiency of vaccines. As a result, the increased investigation into nanoparticles as nano-delivery systems and nanotherapeutics in viral infection, and the development of new and effective methods are essential for inhibiting SARS-CoV-2 infection. In this article, we compare the attributes of several nanoparticles and evaluate their capability to create novel vaccines and treatment methods against different types of viral diseases, especially the SARS-CoV-2 disease.

Graphical Abstract
Recent developments in the probiotics as live biotherapeutic products (LBPs) as modulators of gut brain axis related neurological conditions
Authors: Ağagündüz Duygu , Gençer Bingöl Feray , Çelik Elif , Cemali Özge , Özenir Çiler , Özoğul Fatih , Capasso Raffaele
Published: October 2022

Probiotics have been defined as “living microorganisms that create health benefits in the host when taken in sufficient amounts. Recent developments in the understanding of the relationship between the microbiom and its host have shown evidence about the promising potential of probiotics to improve certain health problems. However, today, there are some confusions about traditional and new generation foods containing probiotics, naming and classifications of them in scientific studies and also their marketing. To clarify this confusion, the Food and Drug Administration (FDA) declared that it has made a new category definition called "live biotherapeutic products" (LBPs). Accordingly, the FDA has designated LBPs as “a biological product that: i)contains live organisms, such as bacteria; ii)is applicable to the prevention, treatment, or cure of a disease/condition of human beings; and iii) is not a vaccine”. The accumulated literature focused on LBPs to determine effective strains in health and disease, and often focused on obesity, diabetes, and certain diseases like inflammatory bowel disease (IBD).However, microbiome also play an important role in the pathogenesis of diseases that age day by day in the modern world via gut-brain axis. Herein, we discuss the novel roles of LBPs in some gut-brain axis related conditions in the light of recent studies. This article may be of interest to a broad readership including those interested in probiotics as LBPs, their health effects and safety, also gut-brain axis.
Inflammatory plasma proteins predict short-term mortality in patients with an acute myocardial infarction
Authors: Schmitz T. , Harmel E. , Heier M. , Peters A. , Linseisen J. , Meisinger C.
Published: October 2022

Background

The aim of this study was to investigate the association between inflammatory markers and 28-day mortality in patients with ST-elevation myocardial infarction (STEMI).

Methods

In 398 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 protein biomarkers were measured in admission arterial blood samples using the OLINK inflammatory panel. In multivariable-adjusted logistic regression models, the association between each marker and 28-day mortality was investigated. The values of the biomarkers most significantly associated with mortality were standardized and summarized to obtain a prediction score for 28-day mortality. The predictive ability of this biomarker score was compared to the established GRACE score using ROC analysis. Finally, a combined total score was generated by adding the standardized biomarker score to the standardized GRACE score.

Results

The markers IL-6, IL-8, IL-10, FGF-21, FGF-23, ST1A1, MCP-1, 4E-BP1, and CST5 were most significantly associated with 28-day mortality, each with FDR-adjusted (false discovery rate adjusted) p-values of < 0.01 in the multivariable logistic regression model. In a ROC analysis, the biomarker score and the GRACE score showed comparable predictive ability for 28-day mortality (biomarker score AUC: 0.7859 [CI: 0.6735–0.89], GRACE score AUC: 0.7961 [CI: 0.6965–0.8802]). By combining the biomarker score and the Grace score, the predictive ability improved with an AUC of 0.8305 [CI: 0.7269–0.9187]. A continuous Net Reclassification Improvement (cNRI) of 0.566 (CI: 0.192–0.94, p-value: 0.003) and an Integrated Discrimination Improvement (IDI) of 0.083 ((CI: 0.016–0.149, p-value: 0.015) confirmed the superiority of the combined score over the GARCE score.

Conclusions

Inflammatory biomarkers may play a significant role in the pathophysiology of acute myocardial infarction (AMI) and AMI-related mortality and might be a promising starting point for personalized medicine, which aims to provide each patient with tailored therapy.
Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways
Authors: Liu Junjun , Liu Mingyuan , Feng Jiaxuan , Zhu Hongqiao , Wu Jianlie , Zhang Heng , Xiao Shun , Jing Zaiping , Zhou Jian , Niu Haitao , Guo Mingjin
Published: October 2022

Abdominal aortic aneurysm (AAA) represents the serious vascular degenerative disorder, which causes high incidence and mortality. Alpha-ketoglutarate (AKG), a crucial metabolite in the tricarboxylic acid (TCA) cycle, has been reported to exert significant actions on the oxidative stress and inflammation. However, its role in AAA still remains elusive. Herein, we examined the effects of AKG on the formation of AAA. The study established an elastase-induced mouse abdominal aortic aneurysms model as well as a TNF-α-mediated vascular smooth muscle cells (VSMCs) model, respectively. We displayed that AKG pre-treatment remarkably prevented aneurysmal dilation assessed by diameter and volume and reduced aortic rupture. In addition, it was also observed that AKG treatment suppressed the development of AAA by attenuating the macrophage infiltration, elastin degradation and collagen fibers remodeling. In vitro, AKG potently decreased TNF-α-induced inflammatory cytokines overproduction, more apoptotic cells and excessive superoxide. Mechanistically, we discovered that upregulation of vpo1 in AAA was significantly suppressed by AKG treatment. By exploring the RNA-seq data, we found that AKG ameliorates AAA mostly though inhibiting oxidative stress and the inflammatory response. PXDN overexpression neutralized the inhibitory effects of AKG on ROS generation and inflammatory reaction in MOVAS. Furthermore, AKG treatment suppressed the expression of p-ERK1/2, 3-Cl Tyr in vivo and in vitro. ERK activator disrupted the protective of AKG on TNF-α-induced VSMCs phenotypic switch. Conclusively, AKG can serve as a beneficial therapy for AAA through regulating PXDN/HOCL/ERK signaling pathways.
Correlates of treatment engagement and client outcomes: results of a randomised controlled trial of nabiximols for the treatment of cannabis use disorder
Authors: Mills Llewellyn , Dunlop Adrian , Montebello Mark , Copeland Jan , Bruno Raimondo , Jefferies Meryem , Mcgregor Iain , Lintzeris Nicholas
Published: October 2022

Introduction and aims

There is increasing interest and evidence for the use of cannabinoid medications in the treatment of cannabis use disorder, but little examination of the correlates of successful treatment. This paper is a secondary analysis of a randomised placebo-controlled trial of nabiximols for the treatment of cannabis use disorder (CUD), aiming to identify which client and treatment characteristics impact treatment engagement and outcomes.

Method

Bayesian multiple regression models were used to examine the impact of age, gender, duration of regular cannabis use, daily quantity of cannabis, cannabis use problems, self-efficacy for quitting, sleep, mental health, pain measures, and treatment group upon treatment engagement (retention, medication dose, and counselling participation) and treatment outcomes (achieving end-of-study abstinence, and a 50% or greater reduction in cannabis use days) among the 128 clients participating in the 12-week trial.

Results

Among the treatment factors, greater counselling attendance was associated with greater odds of abstinence and ≥ 50% reduction in cannabis use; nabiximols with greater odds of ≥ 50% reduction and attending counselling, and reduced hazard of treatment dropout; and higher dose with lower odds of ≥ 50% reduction. Among the client factors, longer duration of regular use was associated with higher odds of abstinence and 50% reduction, and lower hazard of treatment dropout; greater quantity of cannabis use with reduced hazard of dropout, greater odds of attending counselling, and higher average dose; greater pain at baseline with greater odds of ≥ 50% reduction and higher average dose; and more severe sleep issues with lower odds of ≥ 50% reduction. Males had lower odds of attending counselling.

Discussions and conclusions

These findings suggest that counselling combined with agonist pharmacotherapy may provide the optimal treatment for cannabis use disorder. Younger clients, male clients, and clients with sleep issues could benefit from extra support from treatment services to improve engagement and outcomes.

Trial registration

Australian New Zealand Clinical Trials Registry (ACTRN12616000103460)https://www.anzctr.org.au
Post-Acute COVID-19 syndrome (PACS) right atrioventricular and vena cava thrombus on top of a myxoma. A Case report
Authors: Alrifae Ghaliya Mohamed H , Almuquddami Amel Ahmed Said , Etaleb Khaled Masaud , Abdelhamid Mohamed Hadi Mohamed
Published: October 2022

Post-Acute COVID-19 syndrome (PACS) is considered to be one of the least understood post-infectious syndromes. We report a case of a 21-year-old female who had a history of SARS-CoV-2 infection and presented with a right atrioventricular thrombus associated with pulmonary embolism and thrombocytopenia. At the time of admission, she was not vaccinated against SARS-CoV-2, and her serological tests for IgG and IgM antibodies against SARS-CoV-2 were positive. The size of the thrombus measured approximately 6 × 8 × 4 cm, which also led to tricuspid valve insufficiency due to mechanical dilatation of the valve’s ring. The right atrioventricular thrombus also extended up to the inferior vena cava, leading to mild congestive hepatomegaly. Moreover, during thrombectomy, the mass of the thrombus was attached to the interseptal right atrial wall. The histopathological assessment of the core mass revealed that it was a right atrial myxoma hidden inside that large thrombus. We suspect that the formation and propagation of the thrombus to that size occurs as a part of Post-Acute COVID-19 syndrome (PACS). This study reviews and discusses coronavirus disease 2019-relate to thrombus formation inside cardiac chambers in case of a cardiac tumor, like myxoma in the setting of post-acute phase COVID-19 syndrome.
GATA-type transcriptional factor SpGAT1 interacts with SpMIG1 and promotes lipid accumulation in the oleaginous yeast $$Saitozyma \ podzolica$$ zwy-2-3
Authors: Ran Yulu , Xu Hui , Yang Qingzhuoma , Xu Yi , Yang Huahao , Qiao Dairong , Cao Yi
Published: October 2022

Background

In oleaginous yeast, nitrogen limitation is a critical parameter for lipid synthesis. GATA-family transcriptional factor GAT1, a member of the target of rapamycin (TOR) pathway and nitrogen catabolite repression (NCR), regulates nitrogen uptake and utilization. Therefore, it is significant to study the SpGAT1 regulatory mechanism of lipid metabolism for conversion of biomass to microbial oil in $$Saitozyma \ podzolica$$

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Results

Compared with WT, $$\Delta gat1$$

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, and OE::gat1, the lipid yield of OE::gat1 increased markedly in the low carbon and nitrogen ratio (C/N ratio) mediums, while the lipid yield and residual sugar of $$\Delta gat1$$

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decreased in the high C/N ratio medium. According to yeast two-hybrid assays, SpGAT1 interacted with SpMIG1, and its deletion drastically lowered SpMIG1 expression on the high C/N ratio medium. MIG1 deletion has been found in earlier research to affect glucose metabolic capacity, resulting in a prolonged lag period. Therefore, we speculated that SpGAT1 influenced glucose consumption rate across SpMIG1. Based on yeast one-hybrid assays and qRT-PCR analyses, SpGAT1 regulated the glyoxylate cycle genes ICL1, ICL2, and pyruvate bypass pathway gene ACS, irrespective of the C/N ratio. SpGAT1 also could bind to the ACAT2 promoter in the low C/N medium and induce sterol ester (SE) accumulation.

Conclusion

Our findings indicated that SpGAT1 positively regulated lipid metabolism in S.podzolica zwy-2-3, but that its regulatory patterns varied depending on the C/N ratio. When the C/N ratio was high, SpGAT1 interacted with SpMIG1 to affect carbon absorption and utilization. SpGAT1 also stimulated lipid accumulation by regulating essential lipid anabolism genes. Our insights might spur more research into how nitrogen and carbon metabolism interact to regulate lipid metabolism.