bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Outcomes of Combined Phacoemulsification With Intraocular Lens Placement and Microincision Vitrectomy in Adult Vitreoretinal Disease
Authors: Muns Sofía M. , Villegas Victor M. , Murray Timothy G. , Latiff Azeema , Gold Aaron S.
Published: November 2022

Purpose:

To evaluate the safety and clinical outcomes of combined phacoemulsification with intraocular lens (IOL) placement and microincision vitrectomy surgery (MIVS) in adult patients with concomitant cataract and vitreoretinal disease.

Methods:

A consecutive series of patients with comorbid vitreoretinal disease and cataract who had combined phacoemulsification with IOL placement and MIVS was retrospectively analyzed. The main outcome measures were visual acuity (VA) and intraoperative and postoperative complications.

Results:

The analysis comprised 648 eyes of 611 patients. The median follow-up was 26.9 months (range, 12-60 months). The most common vitreoretinal pathology was intraocular tumor (53%). The best-corrected Snellen VA improved from 20/192 at baseline to 20/46 at the 12-month follow-up. The most frequent intraoperative complication was capsule tear (3.9%). The most common postoperative adverse events after 3 months of follow-up (mean, 24 months) were vitreous hemorrhage (3.2%) and retinal detachment (1.8%). No patient developed endophthalmitis.

Conclusions:

Combined phacoemulsification with IOL placement and MIVS is a safe, effective technique to manage a broad range of vitreoretinal diseases in patients with significant cataract.
Amplifying the influence of Māori knowledge in environmental management
Authors: Forster Margaret
Published: November 2022

Modern mapping systems can provide almost everything there is to know about the environment, except what Māori know. So our interests are not that apparent in a mainstream context despite it being widely acknowledged that Māori have a unique and intergenerational relationship with the land- and waterscapes, and the presence of legislative requirements to reflect Māori political agenda in resource management decision-making. He Tātai Whenua is a project that seeks to assemble Māori knowledge and place it alongside existing environmental databases to render this knowledge highly visible and ensure a greater impact on Aotearoa New Zealand rights and environmental regimes. The challenge is constructing a process that maintains the integrity of Māori knowledge as it crosses into domains that are beyond the direct control of Māori communities as kaitiaki, guardians of that knowledge. In this article, He Tātai Whenua is the focal point of discussions around the importance of indigenous leadership, data sovereignty and a social justice agenda to maintain the integrity of Māori knowledge and navigate knowledge boundaries in the research activity. Two approaches are introduced. The first reflects on exchanges between knowledge systems to identify pathways that protect the integrity of Māori knowledge. The second considers how Māori environmental knowledge can be assembled and interact with science in a manner that makes sense from a Māori worldview. Together, these approaches enable us to develop a confidence in collaborative research and increased trust in how research outputs derived from Māori environmental knowledge will be used and applied to realise bicultural spatial governance.
Freedom Highway: Lessons in Courage and Justice From Rhiannon Giddens
Authors: Davis Susan A.
Published: November 2022

General music class is a space for students to engage in honest dialogue and reflection about the societal, cultural, and historical contexts of music, even when the subject matter is difficult. General music teachers can support students by opening “courageous conversations” about race, culture, and complex histories as they intersect with meaningful repertoire. The purpose of this article is to provide music educators with repertoire ideas and resources to assist in the process. Selections from Rhiannon Giddens’ album Freedom Highway are explored as a point of entry for dialogue about race, culture, courage, and justice in the secondary general music classroom. Songs about the Civil War, the Civil Rights era, and the Black Lives Matter movement are linked to inquiry-based strategies and the national music standards.
What respiratory physicians should know about narcolepsy and other hypersomnias
Authors: Klaus Stephen , Carolan Aoife , O'Rourke Deirdre , Kennedy Barry
Published: November 2022

Narcolepsy and related central disorders of hypersomnolence may present to the sleep clinic with excessive daytime sleepiness. A strong clinical suspicion and awareness of the diagnostic clues, such as cataplexy, are essential to avoid unnecessary diagnostic delay. This review provides an overview of the epidemiology, pathophysiology, clinical features, diagnostic criteria and management of narcolepsy and related disorders, including idiopathic hypersomnia, Kleine–Levin syndrome (recurrent episodic hypersomnia) and secondary central disorders of hypersomnolence.
CD206+CD68+ mono-macrophages and serum soluble CD206 level are increased in antineutrophil cytoplasmic antibodies associated glomerulonephritis
Authors: An Xiao-Ning , Wei Zhao-Nan , Xie Yin-Yin , Xu Jing , Shen Yan , Ni Li-Yan , Shi Hao , Shen Ping-Yan , Zhang Wen , Chen Yong-Xi
Published: November 2022

Background

Antineutrophil Cytoplasmic Antibodies (ANCA) associated glomerulonephritis (AGN) is a group of autoimmune diseases and mono-macrophages are involved in its glomerular injuries. In this study, we aim to investigate the role of CD206+ mono-macrophages in AGN.

Methods

27 AGN patients (14 active AGN, 13 remissive AGN) together with healthy controls (n = 9), disease controls (n = 6) and kidney function adjusted controls (n = 9) from Department of Nephrology, Ruijin hospital were recruited. Flow cytometry was used to study proportion of CD206+ cells in peripheral blood. Immunohistochemistry for CD206 staining was performed and CD206 expression was scored in different kidney regions. Serum soluble CD206 (sCD206) was measured by enzyme-linked immunosorbent assay (ELISA). We also generated murine myeloperoxidase (MPO) (muMPO) ANCA by immunizing Mpo−/− mice. Mouse bone marrow-derived macrophages (BMDMs) from wild C57BL/6 mice and peripheral blood mononuclear cell (PBMC) derived macrophages from healthy donors were treated with MPO ANCA with or without its inhibitor AZD5904 to investigate the effects of MPO-ANCA on CD206 expression.

Results

The proportion of peripheral CD206+CD68+ cells in active AGN patients were significantly higher than that in remissive patients (p < 0.001), healthy controls (p < 0.001) and kidney function adjusted controls (p < 0.001). Serum sCD206 level in active AGN patients was higher than that in healthy controls (p < 0.05) and remissive patients (p < 0.01). Immunohistochemistry showed CD206 was highly expressed in different kidney regions including fibrinoid necrosis or crescent formation, glomeruli, periglomerular and tubulointerstitial compartment in active AGN patients in comparison with disease controls. Further studies showed MPO ANCA could induce CD206 expression in BMDMs and PBMC derived macrophages and such effects could be reversed by its inhibitor AZD5904.

Conclusion

ANCA could induce CD206 expression on mono-macrophages and CD206+ mono-macrophages are activated in AGN. CD206 might be involved in the pathogenesis of AAV and may be a potential target for the disease.
Regulatory and effector T cell subsets in tumor-draining lymph nodes of patients with squamous cell carcinoma of head and neck
Authors: Norouzian Marzieh , Mehdipour Fereshteh , Ashraf Mohammad Javad , Khademi Bijan , Ghaderi Abbas
Published: November 2022

Background

A crucial role for the immune system has been proposed in the establishment and progression of head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the cytokine and regulatory profiles of T cells in tumor draining lymph nodes (TDLNs) of patients with HNSCC.

Results

The frequencies of CD4+TNF-α+ and CD4+TNF-αhi negatively were associated with poor prognostic factors such as LN involvement (P = 0.015 and P = 0.019, respectively), stage of the disease (P = 0.032 and P = 0.010, respectively) and tumor size (P = 0.026 and P = 0.032, respectively). Frequencies of CD8+IFN-γ+ and CD8+IFN-γ+ TNF-α+ T cells showed negative relationship with tumor grade (P = 0.035 and P = 0.043, respectively). While, the frequencies of CD4+IL-4+, CD8+IL-10+, CD8+IL-4+T cells were higher in advanced stages of the disease (P = 0.042, P = 0.041 and P = 0.030, respectively) and CD4+IFN-γ+TNF-α−, CD8+IL-4+ and CD8+IFN-γ+TNF-α− T cells were higher in patients with larger tumor size (P = 0.026 and P = 0.032, respectively). Negative associations were found between the frequencies of CD4+CD25+Foxp3+ and CD4+CD25+Foxp3+CD127low/− Treg cells and cancer stage (P = 0.015 and P = 0.059).

Conclusion

This study shed more lights on the changes in immune profile of T cells in TDLNs of HNSCC. Larger tumor size and/or LN involvement were associated with lower frequencies of CD4+TNF-α+, CD8+IFN-γ+ and CD8+IFN-γ+TNF-α+ but higher frequency of CD4+IL-4+ T cells. Moreover, Foxp3+Tregs correlated with good prognostic indicators.
Individual differences among older adults with mild and moderate dementia in social and emotional loneliness and their associations with cognitive and psychological functioning
Authors: Carbone Elena , Piras Federica , Pellegrini Francesca Ferrari , Caffarra Paolo , Borella Erika
Published: November 2022

Background

Loneliness is a major health issue among older adults. The aim of this study was to assess the relationship between loneliness, in its social and emotional facets, and the cognitive (language), and behavioral/psychological functioning as well as quality of life (QoL) in people with mild and moderate dementia, i.e., considering dementia severity as an individual characteristic.

Methods

This cross-sectional study involved 58 people with mild dementia and 55 people with moderate dementia. Participants completed the Social and Emotional Loneliness scale, along with measures assessing their language skills, the frequency and severity of their behavioral and psychological symptoms, and their QoL.

Results

Socio-demographic characteristics and depression, but not loneliness or its social and emotional facets, contributed to explain participants’ behavioral and psychological symptoms, regardless of dementia severity. Loneliness explained, though to a small extent (8% of variance), language skills in people with moderate dementia, with social loneliness only accounting for language skills (18% of variance) in this group. Loneliness also modestly accounted for dysphoria symptoms in both the mildly and moderately impaired (6% and 5% of variance, respectively) individuals with social loneliness predicting dysphoric mood in the former group only (7% of variance). Loneliness also explained, to a larger extent, QoL in both the mildly impaired and moderately impaired individuals (27% and 20% of variance, respectively), its social facet predicting QoL in the mildly impaired (30% of variance), and its emotional facet in the moderately impaired (21% of variance) group.

Conclusion

These findings suggest that loneliness and its facets have a clear impact on perceived QoL, and influence the language skills and dysphoria symptoms of people with dementia, to a degree that depends on dementia severity. The assessment of loneliness and its facets in people with dementia considering dementia severity, and the promotion of social inclusion to reduce it should be considered by professionals.
Dominantly inherited myosin IIa myopathy caused by aberrant splicing of MYH2
Authors: Hedberg-Oldfors Carola , Elíasdóttir Ólöf , Geijer Mats , Lindberg Christopher , Oldfors Anders
Published: November 2022

Background

Myosin heavy chain (MyHC) isoforms define the three major muscle fiber types in human extremity muscles. Slow beta/cardiac MyHC (MYH7) is expressed in type 1 muscle fibers. MyHC IIa (MYH2) and MyHC IIx (MYH1) are expressed in type 2A and 2B fibers, respectively. Whereas recessive MyHC IIa myopathy has been described in many cases, myopathy caused by dominant MYH2 variants is rare and has been described with clinical manifestations and muscle pathology in only one family and two sporadic cases.

Methods

We investigated three patients from one family with a dominantly inherited myopathy by clinical investigation, whole-genome sequencing, muscle biopsy, and magnetic resonance imaging (MRI).

Results

Three siblings, one woman and two men now 54, 56 and 66 years old, had experienced muscle weakness initially affecting the lower limbs from young adulthood. They have now generalized proximal muscle weakness affecting ambulation, but no ophthalmoplegia. Whole-genome sequencing identified a heterozygous MYH2 variant, segregating with the disease in the three affected individuals: c.5673 + 1G > C. Analysis of cDNA confirmed the predicted splicing defect with skipping of exon 39 and loss of residues 1860–1891 in the distal tail of the MyHC IIa, largely overlapping with the filament assembly region (aa1877–1905). Muscle biopsy in two of the affected individuals showed prominent type 1 muscle fiber predominance with only a few very small, scattered type 2A fibers and no type 2B fibers. The small type 2A fibers were frequently hybrid fibers with either slow MyHC or embryonic MyHC expression. The type 1 fibers showed variation in fiber size, internal nuclei and some structural alterations. There was fatty infiltration, which was also demonstrated by MRI.

Conclusion

Dominantly inherited MyHC IIa myopathy due to a splice defect causing loss of amino acids 1860–1891 in the distal tail of the MyHC IIa protein including part of the assembly competence domain. The myopathy is manifesting with slowly progressive muscle weakness without overt ophthalmoplegia and markedly reduced number and size of type 2 fibers.
Reversible Pisa syndrome caused by chronic subdural hematoma in a patient with Parkinson’s disease: a case report
Authors: Igami Eriko , Fujimaki Motoki , Shimizu Mai , Ishiguro Yuta , Kodama Takuma , Okuma Yasuyuki , Hattori Nobutaka , Noda Kazuyuki
Published: November 2022

Background

Pisa syndrome (PS), characterized by lateral trunk flexion, is quite common in patients with Parkinson’s disease (PD). Patients with PS are older and have a significantly longer disease duration, more severe motor phenotype, ongoing combined treatment with levodopa and dopamine agonists, and higher levodopa equivalent daily dose. We describe here, to the best of our knowledge, the first case of a woman with PD who developed acute-onset PS caused by chronic subdural hematoma (CSDH).

Case presentation

A 70-year-old woman developed acute-onset lateral flexion of her trunk to the left side while standing, and she was admitted to our hospital. One month before, she had a mild head trauma with loss of consciousness. At 65 years of age, she noticed difficulty with walking and clumsiness with her hands. She was diagnosed as having PD (Hoehn and Yahr stage 2) and levodopa was initiated. Her symptoms were markedly improved. At 67 years of age, she developed orthostatic hypotension and was treated sequentially with fluids, compression stockings, and midodrine. Urgently performed brain computed tomography (CT) showed a CSDH in the right hemisphere resulting in a marked compression of the hemisphere. After surgical evacuation, her PS disappeared. She has fully recovered to her preoperative level of function.

Conclusion

The present case provides a valuable insight, that is, the mesial frontal lobe and its connections from the posterior parietal cortex play crucial roles in maintaining the body schema and in the pathophysiology of PS. This case suggests that CSDH should be considered when clinicians examine acute-onset PS, even in patients with neurodegenerative disorders such as PD. Appropriate patient triage and timely neurosurgical intervention should be considered.
Clinicopathological features of patients with wide local excision of eyelid malignant neoplasms: a more than five years retrospective study from China
Authors: Han Yuanyuan , Kong Miao , Luo Yan , Sun Bin , Wang Zhiqiang , Zhang Hong
Published: November 2022

Background

To investigate the correlation between the clinical and pathological characteristics and outcomes in patients with eyelid malignant tumors underwent wide local excision.

Methods

This retrospective study included 141 cases of eyelid malignant neoplasms from January 2010 to December 2015 in Shanxi eye hospital. Demographic and clinical information were collected. The Kaplan–Meier method was used to calculate survival curves, and the log-rank test method was used to compare survival between groups. Cox proportional regression models were used to calculate the hazard ratios (HR) of total recurrence rate and metastasis rate.

Results

Overall, there were 141 eyelid malignant neoplasms cases aged 65.34 ± 9.69 (range, 41—88) years old. The duration time range was from 1 to 828 (61.09 ± 122.21) months. Basal cell carcinoma (BCC) is the most common of all eyelid malignancies, accounting for 84 (59.5%), followed by Sebaceous gland carcinoma (SGC, 41, 29%), Squamous Cell Carcinoma (SCC, 11, 7.8%), Malignant Melanoma (MM, 3, 2.1%)。On cox-regression analysis, pathological classification (HR 1.959; 95% CI 1.012–3.790;p = 0.046) and eyelid tumor surgery history (HR 17.168; 95% CI 1.889–156.011;p = 0.012) were independently associated with recurrence in patients with eyelid malignant neoplasm. Pathological classification (HR 2.177; 95% CI 1.423 -3.331;p < 0.001) was independently associated with metastasis in patients with eyelid malignant neoplasm. Recurrence and metastasis were most likely to occur in 3 years after surgery.

Conclusion

Wide local excision is an effective and economical treatment for eyelid malignant neoplasms. The prognosis is mainly related to pathological types, eyelid tumor surgical history and TNM stages.
ADHD in adults with major depressive or bipolar disorder: does it affect clinical features, comorbidity, quality of life, and global functioning?
Authors: Sadeghian Nadooshan Mohammad Reza , Shahrivar Zahra , Mahmoudi Gharaie Javad , Salehi Leyla
Published: November 2022

Background

This study compared clinical characteristics, concurrent disorders, level of function, and quality of life in adults with bipolar (BD) or major depressive disorder (MDD) in those with/without adult attention defici1t hyperactivity disorder (AADHD).

Methods

The participants were recruited among adult inpatients and outpatients with MDD or BD in their current partial remission in a psychiatric hospital. They were evaluated using the interview for adults with ADHD (DIVA-5), Conners’ Adult ADHD Rating Scales–Self-Report-Screening Version (CAARS-SR-SV), Structured Clinical Interview for DSM-V (SCID-5), Beck Depression Inventory-II and Young Mania Rating Scale, Global Assessment of Functioning (GAF) and World Health Organization Quality of Life Scale-Brief (WHOQoL-BREF).

Results

In those with MDD (n = 105) and BD (n = 103), AADHD was detected as 13.3% and 16.5%, respectively. The inattentive presentation was the most prevalent type among patients with AADHD. Compared to the patients without AADHD, the results regarding the prevalence of comorbidities, suicidal attempts, severity of affective episodes, the early emergence of the affective disorders, and level of quality of life and global functioning were poorer in the group with AADHD (p < 0.05).

Limitations

The participants were individuals with major depressive or bipolar type I disorder with a mostly manic episode, chosen among the referrals to a tertiary psychiatric hospital with high comorbidity and more severe psychopathology. This may limit the generalizability of the findings.

Conclusion

ADHD was common in adults with MDD and BD, along with high psychiatric comorbidity and negative consequences. Clinicians are suggested to screen adults with mood disorders for the symptoms of ADHD for a more precise and comprehensive diagnosis and to provide a more appropriate therapeutic intervention.
Prostate-specific antigen nadir within 1 year of radiotherapy combined with hormone therapy predicts cancer-specific mortality and biochemical recurrence-free survival in prostate cancer patients
Authors: Cetin Ilknur Alsan , Akay Sıtkı Utku , Sengoz Meric
Published: November 2022

Background

In this study, we investigated the ability of prostate-specific antigen (PSA) 12 months after (nPSA12) external beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT) to predict biochemical recurrence-free survival (BRFS), overall survival (OS), and prostate cancer-specific mortality (PCSM) in intermediate- and high-risk prostate cancer patients.

Methods

We retrospectively reviewed the clinical data of 338 intermediate- and high-risk prostate cancer patients treated with EBRT with ADT at our institution between 2000 and 2018. The median radiation dose was 76 Gy, the median initial PSA level was 17 ng/mL (range, 1–228 ng/mL), and the median duration of ADT was 24 months (range, 6–167 months). The median PSA level 1 months after EBRT was 0.06 ng/mL (range, 0–25.6 ng/mL). Univariate and multivariate analyses were performed. Patient survival was assessed using the Kaplan-Meier method and Cox proportional hazards regression analyses.

Results

The median follow-up time was 5 years (range, 1–20 years). Multivariate analysis revealed that nPSA was an independent and significant factor associated with OS, PCSM, and BRFS (P = 0.008, P = 0.001, P = 0.04). Furthermore, the time to nPSA12 was an independent predictor of PCSM and BRFS (P = 0.042, P = 0.021). Pelvic irradiation was also significantly associated with worse OS and PCSM (P = 0.004, P = 0.01). Additionally, age (≤ 70 or > 70 years) and hormone therapy duration (6 months, 1–3 years, or > 3 years) were significantly associated with OS and PCSM, respectively (P = 0.004, P = 0.02). For high risk, nPSA and nPSA12 were an independent predictor for BRFS. (P = 0.021, P = 0.029)

Conclusion

The nPSA12 level of > 0.06 ng/mL may independently predict worse PCSM and BRFS in intermediate- and high-risk prostate cancer patients undergoing EBRT and ADT. Additionally, for high risk, nPSA > 0.06 ng/mL and nPSA12 > 0.06 ng/mL may independently predict worse BRFS.
Infective endocarditis: association between origin of causing bacteria and findings during oral infection screening
Authors: Thoresen Therese , Jordal Stina , Lie Stein- Atle , Wünsche Friederike , Jacobsen Martha Rolland , Lund Bodil
Published: November 2022

Background

Oral streptococci represent the causing microorganism for infective endocarditis (IE) in many patients. The impact of oral infections is questioned, and it has been suggested that bacteraemia due to daily routines may play a bigger part in the aetiology of IE. The aim of this study was to examine the association between oral health and infective endocarditis caused by oral bacteria in comparison with bacteria of other origin than the oral cavity.

Methods

A retrospective study was conducted at Haukeland University Hospital from 2006- 2015. All consecutive adult patients admitted to hospital for treatment of IE and subjected to an oral focus screening including orthopantomogram, were included. The clinical, radiological and laboratory characteristics of the patients, collected during oral infectious focus screening, were analysed. Patient survival was calculated using Kaplan–Meier and mortality rates were compared using Cox-regression.

Results

A total of 208 patients were included, 77% (n = 161) male patients and 23% (n = 47) female, mean age was 58 years. A total of 67 (32%) had IE caused by viridans streptococci. No statistically significant correlation could be found between signs of oral infection and IE caused by viridans streptococci. The overall mortality at 30 days was 4.3% (95% CI: 1.6–7.0). There was no statistical difference in mortality between IE caused by viridans streptococci or S. aureus (HRR = 1.16, 95% CI: 0.57–2.37, p = 0.680).

Conclusion

The study indicates that the association between origin of the IE causing bacteria and findings during oral infection screening might be uncertain and may suggest that the benefit of screening and elimination of oral infections in patients admitted with IE might be overestimated. However, the results should be interpreted with caution and further studies are needed before any definite conclusions can be drawn.
How is modern bedside teaching structured? A video analysis of learning content, social and spatial structures
Authors: Blaschke Anna-Lena , Rubisch Hannah P. K. , Schindler Ann-Kathrin , Berberat Pascal O. , Gartmeier Martin
Published: November 2022

Background

Bedside teaching (BST) is an essential and traditional clinical teaching format. It has been subject to various impediments and has transformed over time. Besides a decrease in bedside time, there has also been a didactic diversification. In order to use time at the bedside effectively and understand the current design of BST, we here offer an evidence-based insight into how BST is practiced. This may serve as a basis for a refinement of its didactic design.

Methods

In the current study, we investigate the interrelationships between learning content and the social as well as spatial structures of BST. To this end, we have empirically analysed almost 80 hours of video material from a total of 36 BST sessions with good interrater reliability.

Results

BST lasted on average 125 min, most of which was spent in plenary and less than a third of the time at the patient’s bedside. History taking was primarily practiced at the bedside while case presentations, clinical reasoning and theoretical knowledge were largely taught away from the patient. Clinical examination took place to a similar extent in the patient’s room and in the theory room.

Conclusions

Even though the filmed BSTs are not purely “bedside”, the teaching format investigated here is a typical example of undergraduate medical education. In order to maximize the teaching time available, a suitable learning space should be provided in addition to the bedside. Moreover, the clinical examination should be revised in its general sequence prior to the BST, and conscious decisions should be made regarding the social structure so as to optimize the potential of small groups and plenary sessions.
In silico clinical trials for relapsing-remitting multiple sclerosis with MS TreatSim
Authors: Sips Fianne L. P. , Pappalardo Francesco , Russo Giulia , Bursi Roberta
Published: November 2022

Background

The last few decades have seen the approval of many new treatment options for Relapsing-Remitting Multiple Sclerosis (RRMS), as well as advances in diagnostic methodology and criteria. These developments have greatly improved the available treatment options for today’s Relapsing-Remitting Multiple Sclerosis patients. This increased availability of disease modifying treatments, however, has implications for clinical trial design in this therapeutic area. The availability of better diagnostics and more treatment options have not only contributed to progressively decreasing relapse rates in clinical trial populations but have also resulted in the evolution of control arms, as it is often no longer sufficient to show improvement from placebo. As a result, not only have clinical trials become longer and more expensive but comparing the results to those of “historical” trials has also become more difficult.

Methods

In order to aid design of clinical trials in RRMS, we have developed a simulator called MS TreatSim which can simulate the response of customizable, heterogeneous groups of patients to four common Relapsing-Remitting Multiple Sclerosis treatment options. MS TreatSim combines a mechanistic, agent-based model of the immune-based etiology of RRMS with a simulation framework for the generation and virtual trial simulation of populations of digital patients.

Results

In this study, the product was first applied to generate diverse populations of digital patients. Then we applied it to reproduce a phase III trial of natalizumab as published 15 years ago as a use case. Within the limitations of synthetic data availability, the results showed the potential of applying MS TreatSim to recreate the relapse rates of this historical trial of natalizumab.

Conclusions

MS TreatSim’s synergistic combination of a mechanistic model with a clinical trial simulation framework is a tool that may advance model-based clinical trial design.
The challenges facing programs for the prevention and control of non-communicable diseases in Iran: a qualitative study of senior managers' viewpoints
Authors: Partovi Yegane , Farahbakhsh Mostafa , Tabrizi Jafar Sadegh , Gholipour Kamal , Koosha Ahmad , Sharbafi Jabreil , Wilson Andrew
Published: November 2022

Background

Despite significant achievements in the prevention and control of NCDs in Iran, these conditions are still the biggest challenges to Iran's healthcare system and are estimated to account for 78.1 percent of all deaths. Therefore, this study aimed to reflect on the potential challenges standing in the way to implement the relevant policies, empower the dimensions of governance, and react in an effective and timely manner by Iran's healthcare system to NCDs.

Methods

This study was conducted with a qualitative approach using the conventional content analysis method. A total of 46 senior managers involved in the prevention and control of NCDs at the medical sciences universities across Iran were recruited through the purposive sampling method and were interviewed via semi-structured interviews. Graneheim and Lundman's approach was utilized to analyze the data.

Results

According to the analysis of the senior managers' viewpoints, current challenges to implement the program for the prevention and control of NCDs in Iran could be placed into six main categories, including financing, human resources, infrastructure and inputs, legal, executive, administrative, as well as inter-sectoral collaboration, and management and policy-making challenges with their own sub-categories.

Conclusion

The results revealed that financing was the biggest challenge to successfully implementing the program for the prevention and control of NCDs in Iran. However, strengthening Iran's healthcare system in the field of the prevention of NCDs demanded more innovative measures and strategies, such as the empowerment of human resources, the effective use of intra- and inter-sectoral collaboration, and non-governmental organizations and charities, along with the exploitation of evidence-based studies during policy-making and decision-making processes, with no need for financial resources.
Assessing the feasibility of sustaining SARS-CoV-2 local containment in China in the era of highly transmissible variants
Authors: Wang Yan , Sun Kaiyuan , Feng Zhaomin , Yi Lan , Wu Yanpeng , Liu Hengcong , Wang Quanyi , Ajelli Marco , Viboud Cécile , Yu Hongjie
Published: November 2022

Background

The SARS-CoV-2 containment strategy has been successful in mainland China prior to the emergence of Omicron. However, in the era of highly transmissible variants, whether it is possible for China to sustain a local containment policy and under what conditions China could transition away from it are of paramount importance at the current stage of the pandemic.

Methods

We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining SARS-CoV-2 local containment in mainland China considering the Omicron variants, China’s current immunization level, and nonpharmaceutical interventions (NPIs). We also built a statistical model to estimate the overall disease burden under various hypothetical mitigation scenarios.

Results

We found that due to high transmissibility, neither Omicron BA.1 nor BA.2 could be contained by China’s pre-Omicron NPI strategies which were successful prior to the emergence of the Omicron variants. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success. We estimated that an acute Omicron epidemic wave in mainland China would result in significant number of deaths if China were to reopen under current vaccine coverage with no antiviral uptake, while increasing vaccination coverage and antiviral uptake could substantially reduce the disease burden.

Conclusions

As China’s current vaccination has yet to reach high coverage in older populations, NPIs remain essential tools to maintain low levels of infection while building up protective population immunity, ensuring a smooth transition out of the pandemic phase while minimizing the overall disease burden.
Risk for newly diagnosed diabetes after COVID-19: a systematic review and meta-analysis
Authors: Zhang Ting , Mei Qimin , Zhang Zhaocai , Walline Joseph Harold , Liu Yecheng , Zhu Huadong , Zhang Shuyang
Published: November 2022

Background

There is growing evidence that patients recovering after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may have a variety of acute sequelae including newly diagnosed diabetes. However, the risk of diabetes in the post-acute phase is unclear. To solve this question, we aimed to determine if there was any association between status post-coronavirus disease (COVID-19) infection and a new diagnosis of diabetes.

Methods

We performed a systematic review and meta-analysis of cohort studies assessing new-onset diabetes after COVID-19. PubMed, Embase, Web of Science, and Cochrane databases were all searched from inception to June 10, 2022. Three evaluators independently extracted individual study data and assessed the risk of bias. Random-effects models estimated the pooled incidence and relative risk (RR) of diabetes compared to non-COVID-19 after COVID-19.

Results

Nine studies with nearly 40 million participants were included. Overall, the incidence of diabetes after COVID-19 was 15.53 (7.91–25.64) per 1000 person-years, and the relative risk of diabetes after COVID-19 infection was elevated (RR 1.62 [1.45–1.80]). The relative risk of type 1 diabetes was RR=1.48 (1.26–1.75) and type 2 diabetes was RR=1.70 (1.32–2.19), compared to non-COVID-19 patients. At all ages, there was a statistically significant positive association between infection with COVID-19 and the risk of diabetes: <18 years: RR=1.72 (1.19–2.49), ≥18 years: RR=1.63 (1.26–2.11), and >65 years: RR=1.68 (1.22–2.30). The relative risk of diabetes in different gender groups was about 2 (males: RR=2.08 [1.27–3.40]; females: RR=1.99 [1.47–2.80]). The risk of diabetes increased 1.17-fold (1.02–1.34) after COVID-19 infection compared to patients with general upper respiratory tract infections. Patients with severe COVID-19 were at higher risk (RR=1.67 [1.25–2.23]) of diabetes after COVID-19. The risk (RR=1.95 [1.85–2.06]) of diabetes was highest in the first 3 months after COVID-19. These results remained after taking confounding factors into account.

Conclusions

After COVID-19, patients of all ages and genders had an elevated incidence and relative risk for a new diagnosis of diabetes. Particular attention should be paid during the first 3 months of follow-up after COVID-19 for new-onset diabetes.
Impact of upper and lower respiratory symptoms on COVID-19 outcomes: a multicenter retrospective cohort study
Authors: Nakagawara Kensuke , Chubachi Shotaro , Namkoong Ho , Tanaka Hiromu , Lee Ho , Azekawa Shuhei , Otake Shiro , Fukushima Takahiro , Morita Atsuho , Watase Mayuko , Sakurai Kaori , Kusumoto Tatsuya , Asakura Takanori , Masaki Katsunori , Kamata Hirofumi , Ishii Makoto , Hasegawa Naoki , Harada Norihiro , Ueda Tetsuya , Ueda Soichiro , Ishiguro Takashi , Arimura Ken , Saito Fukuki , Yoshiyama Takashi , Nakano Yasushi , Mutoh Yoshikazu , Suzuki Yusuke , Edahiro Ryuya , Murakami Koji , Sato Yasunori , Okada Yukinori , Koike Ryuji , Kitagawa Yuko , Tokunaga Katsushi , Kimura Akinori , Imoto Seiya , Miyano Satoru , Ogawa Seishi , Kanai Takanori , Fukunaga Koichi
Published: November 2022

Background

Respiratory symptoms are associated with coronavirus disease 2019 (COVID-19) outcomes. However, the impacts of upper and lower respiratory symptoms on COVID-19 outcomes in the same population have not been compared. The objective of this study was to characterize upper and lower respiratory symptoms and compare their impacts on outcomes of hospitalized COVID-19 patients.

Methods

This was a multicenter, retrospective cohort study; the database from the Japan COVID-19 Task Force was used. A total of 3314 COVID-19 patients were included in the study, and the data on respiratory symptoms were collected. The participants were classified according to their respiratory symptoms (Group 1: no respiratory symptoms, Group 2: only upper respiratory symptoms, Group 3: only lower respiratory symptoms, and Group 4: both upper and lower respiratory symptoms). The impacts of upper and lower respiratory symptoms on the clinical outcomes were compared. The primary outcome was the percentage of patients with poor clinical outcomes, including the need for oxygen supplementation via high-flow oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation or death.

Results

Of the 3314 COVID-19 patients, 605, 1331, 1229, and 1149 were classified as Group 1, Group 2, Group 3, and Group 4, respectively. In univariate analysis, patients in Group 2 had the best clinical outcomes among all groups (odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.11–0.39), while patients in Group 3 had the worst outcomes (OR: 3.27, 95% CI: 2.43–4.40). Group 3 patients had the highest incidence of pneumonia, other complications due to secondary infections, and thrombosis during the clinical course.

Conclusions

Upper and lower respiratory tract symptoms had vastly different impacts on the clinical outcomes of COVID-19.
Increased chest CT derived bone and muscle measures capture markers of improved morbidity and mortality in COPD
Authors: Wilson Ava C. , Bon Jessica M. , Mason Stephanie , Diaz Alejandro A. , Lutz Sharon M. , Estepar Raul San Jose , Kinney Gregory L. , Hokanson John E. , Rennard Stephen I. , Casaburi Richard , Bhatt Surya P. , Irvin Marguerite R. , Hersh Craig P. , Dransfield Mark T. , Washko George R. , Regan Elizabeth A. , McDonald Merry-Lynn
Published: November 2022

Background

Chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging and is associated with comorbid conditions including osteoporosis and sarcopenia. These extrapulmonary conditions are highly prevalent yet frequently underdiagnosed and overlooked by pulmonologists in COPD treatment and management. There is evidence supporting a role for bone-muscle crosstalk which may compound osteoporosis and sarcopenia risk in COPD. Chest CT is commonly utilized in COPD management, and we evaluated its utility to identify low bone mineral density (BMD) and reduced pectoralis muscle area (PMA) as surrogates for osteoporosis and sarcopenia. We then tested whether BMD and PMA were associated with morbidity and mortality in COPD.

Methods

BMD and PMA were analyzed from chest CT scans of 8468 COPDGene participants with COPD and controls (smoking and non-smoking). Multivariable regression models tested the relationship of BMD and PMA with measures of function (6-min walk distance (6MWD), handgrip strength) and disease severity (percent emphysema and lung function). Multivariable Cox proportional hazards models were used to evaluate the relationship between sex-specific quartiles of BMD and/or PMA derived from non-smoking controls with all-cause mortality.

Results

COPD subjects had significantly lower BMD and PMA compared with controls. Higher BMD and PMA were associated with increased physical function and less disease severity. Participants with the highest BMD and PMA quartiles had a significantly reduced mortality risk (36% and 46%) compared to the lowest quartiles.

Conclusions

These findings highlight the potential for CT-derived BMD and PMA to characterize osteoporosis and sarcopenia using equipment available in the pulmonary setting.
Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms
Authors: Vergès Bruno , Aboyans Victor , Angoulvant Denis , Boutouyrie Pierre , Cariou Bertrand , Hyafil Fabien , Mohammedi Kamel , Amarenco Pierre
Published: November 2022

Several randomized controlled trials have demonstrated the benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on ischemic stroke in patients with diabetes. In this review, we summarize and discuss the potential mechanisms of stroke protection by GLP-1RAs. GLP-1RAs exert multiple anti-atherosclerotic effects contributing to stroke prevention such as enhanced plaque stability, reduced vascular smooth muscle proliferation, increased nitric oxide, and improved endothelial function. GLP-1RAs also lower the risk of stroke by reducing traditional stroke risk factors including hyperglycemia, hypertension, and dyslipidemia. Independently of these peripheral actions, GLP-1RAs show direct cerebral effects in animal stroke models, such as reduction of infarct volume, apoptosis, oxidative stress, neuroinflammation, excitotoxicity, blood–brain barrier permeability, and increased neurogenesis, neuroplasticity, angiogenesis, and brain perfusion. Despite these encouraging findings, further research is still needed to understand more thoroughly the mechanisms by which GLP-1RAs may mediate stroke protection specifically in the human diabetic brain.
Biosensing chips for cancer diagnosis and treatment: a new wave towards clinical innovation
Authors: Iqbal Muhammad Javed , Javed Zeeshan , Herrera-Bravo Jesús , Sadia Haleema , Anum Faiza , Raza Shahid , Tahir Arifa , Shahwani Muhammad Naeem , Sharifi-Rad Javad , Calina Daniela , Cho William C.
Published: November 2022

Recent technological advances in nanoscience and material designing have led to the development of point-of-care devices for biomolecule sensing and cancer diagnosis. In situ and portable sensing devices for bedside, diagnosis can effectively improve the patient’s clinical outcomes and reduce the mortality rate. Detection of exosomal RNAs by immuno-biochip with increased sensitivity and specificity to diagnose cancer has raised the understanding of the tumor microenvironment and many other technology-based biosensing devices hold great promise for clinical innovations to conquer the unbeatable fort of cancer metastasis. Electrochemical biosensors are the most sensitive category of biomolecule detection sensors with significantly low concentrations down to the atomic level. In this sense, this review addresses the recent advances in cancer detection and diagnosis by developing significant biological sensing devices that are believed to have better sensing potential than existing facilities.
Induction of oxidative DNA damage, cell cycle arrest and p53 mediated apoptosis by calcium titanate nanoparticles in MCF-7 breast cancer cells
Authors: Mohamed Hanan R. H. , Ibrahim Maria M. H. , Diab Ayman
Published: November 2022

Background

The distinctive properties and high activity of calcium titanate nanoparticles (CaTiO3-NPs) increase their use in many products. However, the cytotoxic and genotoxic effects of CaTiO3-NPs in human cancer cell lines have not been well studied. Therefore, this study was conducted to explore CaTiO3-NPs induced cytotoxicity, genomic instability and apoptosis in human breast cancer (MCF-7) cells.

Methods

Sulforhodamine B (SRB) and the alkaline comet assays were done to study cell viability and DNA damage induction, respectively. Apoptosis induction and cell cycle distribution were analyzed using flow cytometry. The level of intracellular reactive oxygen species (ROS) was studied, and the expression levels of p53, Bax and Bcl2 genes were also measured.

Results

The results of the Sulforhodamine B (SRB) cytotoxicity assay showed that viability of MCF-7 cells was not affected by CaTiO3-NPs treatment for 24 h, however, exposure to CaTiO3-NPs for 72 h caused concentrations dependent death of MCF-7 cells. Treatment with CaTiO3-NPs for 72 h caused marked increases in intracellular ROS level and induced DNA damage. Treatment of MCF-7 cells with CaTiO3-NPs also caused MCF-7 cell cycle arrest at the G0 and S phases and s triggered apoptosis of MCF-7 cells by causing simultaneous increases in the expression levels of apoptotic p53 and Bax genes and a decrease in the expression level of anti-apoptotic Bcl2 gene.

Conclusion

Collectively, it was concluded that CaTiO3-NPs cause time- and concentration-dependent cytotoxic effects in human MCF-7 cells through induction of ROS generation, genomic instability and apoptosis. Thus it is recommended that further in vitro and in vivo studies are therefore recommended to understand the cytotoxic and biological effects of CaTiO3-NPs.
Agreement between 24-hour urine and 24-hour food recall in measuring salt intake in primary school children in Australia
Authors: Santos Joseph Alvin , Bolton Kristy A. , Rosewarne Emalie , Trieu Kathy , Di Tanna Gian Luca , Woodward Mark , Webster Jacqui , Grimes Carley
Published: November 2022

Background

Monitoring salt consumption in children is essential for informing and implementing public health interventions to reduce children’s salt intake. However, collection of 24-hour urines, considered as the most reliable approach, can be especially challenging to school children. This study aimed to assess the agreement between 24-hour urine (24hrU) and 24-hour food recall (24hrFR) in: (1) estimating salt intake in children; (2) classifying salt intakes above the recommended upper level set for children, and; (3) estimating change in mean salt intake over time.

Methods

This study utilised data from two cross-sectional surveys of school children aged 8 to 12 years living in the state of Victoria, Australia. A single 24hrU and 24hrFR were collected from each participant. Suspected inaccurate urine collections and implausible energy intakes were excluded based on pre-defined criteria. The agreement between the two methods was assessed using Bland-Altman methodology, the intraclass correlation coefficient (ICC), and the kappa statistic. The difference between the measured change in salt intake over time using 24hrU and 24hrFR was derived using mixed effects linear regression analysis.

Results

A total of 588 participants provided a 24hrU and 24hrFR. Overall, there was no meaningful difference in mean estimated salt intake between the two methods (− 0.2 g/day, 95% CI − 0.5 to 0.1). The Bland-Altman plot showed wide 95% limits of agreement (− 7.2 to 6.8). The ICC between the two methods was 0.13 (95% CI 0.05 to 0.21). There was poor interrater reliability in terms of classifying salt intake above the recommended upper level for children, with an observed agreement of 63% and kappa statistic of 0.11. The change in mean salt intake over time was 0.2 g/day (− 0.4 to 0.7) based on 24hrU, and 0.5 g/day (− 0.0 to 1.1) based on 24hrFR, with a difference-in-differences of 0.4 g/day (− 0.3 to 1.1).

Conclusions

24hrFR appears to provide a reasonable estimate of mean salt intake as measured by 24hrU in Australian school children. However, similar to previous observations in adults, and of studies exploring other alternative methods for estimating salt intake, 24hrFR is a poor predictor of individual-level salt intake in children.