bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractSeveral 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

AbstractRecent 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.