bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual outcomes of observation, macular laser and anti-VEGF in diabetic macular edema in type 1 diabetes: a real-world study
Authors: Wirkkala Joonas , Kubin Anna-Maria , Ohtonen Pasi , Yliselä Joona , Siik Taru , Hautala Nina
Published: June 2022

Background

The treatment for diabetic macular edema (DME) has revolutionized during the last 15 years after the introduction of intravitreal anti-VEGF agents. The aim of the current study is to evaluate the real-world visual outcomes of diabetic macular edema (DME) treatment in patients with type 1 diabetes (T1D) in long-term follow-up.

Methods

A real-world, descriptive, population-based cohort and follow-up of all patients with T1D and DME in 2006-2020 in 34 communities of the Northern Ostrobothnia Hospital District. The main outcome measures included age, gender, duration of T1D at the onset of DME, stage of retinopathy, treatment of DME (observation, laser, intravitreal treatments, combination), and visual outcomes.

Results

A total of 304 eyes of 206 T1D patients with DME were included. 75% (n=155) had non-proliferative diabetic retinopathy during the onset of DME. 15% of the cases were observed, 33% had macular laser, 41% intravitreal anti-VEGF and 12% combination of laser and intravitreal injections. Patients in anti-VEGF and in combination groups gained 4.9 and 5.5 ETDRS letters after the initial DME episode (p<0.001 and p<0.001), and the long-term visual improvements were 4.1 and 5.1 ETDRS letters (p<0.001 and p<0.001), respectively. In observation and laser groups the initial gain of 0.1 (p>0.90) and loss of 0.4 ETDRS letter (p=0.61), respectively, was noted. After the follow-up, a 3.7 ETDRS letter decrease was documented in the observation group (p>0.90) and a 1.1 (p=0.14) ETDRS letter decline in the laser group of patients. At the beginning of treatment, eyes subjected to anti-VEGF alone or in combination with laser had lower visual acuity compared to eyes subjected to observation or macular laser. The average of a 6.1±4.8 anti-VEGF injections were needed to dry DME. Visual impairment due to DME decreased from 2.4% to 1.0% during the 15-year period.

Conclusions

Anti-VEGF alone or in combination with macular laser seems to be beneficial in terms of visual outcomes and treatment stability in T1D patients with central DME.

Moreover, satisfying long-term visual outcomes were achieved with anti-VEGF treatment in a real-world setting.
Inequalities in the prevalence of stunting, anemia and exclusive breastfeeding among African children
Authors: Ekholuenetale Michael , Okonji Osaretin Christabel , Nzoputam Chimezie Igwegbe , Barrow Amadou
Published: June 2022

Background

Childhood stunting and anemia are on the increase in many resource-constrained settings, without a counter increase in proper feeding practices such as exclusive breastfeeding. The objective of this study was to explore the prevalence of stunting, anemia and exclusive breastfeeding across African countries.

Methods

Demographic and Health Survey (DHS) data from 39 African countries was analyzed. Data from under 5 children were analyzed. Forest plot was used to determine inequalities in the prevalence of the outcome variables.

Results

The prevalence of stunting was highest in Burundi (56%), Madagascar (50%) and Niger (44%). In addition, Burkina Faso (88%), Mali (82%), Cote d’Ivoire and Guinea (75% each) and Niger (73%) had the highest prevalence of anemia. Furthermore, Burundi (83%), Rwanda (81%) and Zambia (70%) had the highest exclusive breastfeeding. We found statistical significant difference in the prevalence of stunting, anemia and exclusive breastfeeding (p < 0.001). Higher prevalence of stunting and anemia were estimated among the male, rural residents, those having mothers with low education and from poor household wealth.

Conclusion

Concerted efforts are required to improve childhood health, survival and proper feeding practice. Reduced stunting and anemia could be achieved through sustained socioeconomic improvement that is shared in equity and equality among the population. Interventions aimed at increasing food availability can also aid in the reduction of hunger, particularly in impoverished communities.
Study protocol: cohort event monitoring for safety signal detection after vaccination with COVID-19 vaccines in Iran
Authors: Aliyari Roqayeh , Mahdavi Sepideh , Enayatrad Mostafa , Sahab-Negah Sajad , Nili Sairan , Fereidooni Mohammad , Mangolian shahrbabaki Parvin , Ansari-Moghaddam Alireza , Heidarzadeh Abtin , Shahraki-Sanavi Fariba , Amini Moridani Mohammadreza , Fateh Mansooreh , Khajeha Hamidreza , Emamian Zahra , Behmanesh Elahe , Sharifi Hamid , Emamian Mohammad Hassan
Published: June 2022

Background

New vaccines that are initially approved in clinical trials are not completely free of risks. Systematic vaccine safety surveillance is required for ensuring safety of vaccines. This study aimed to provide a protocol for safety monitoring of COVID-19 vaccines, including Sputnik V, Sinopharm (BBIBP-CorV), COVIran Barekat, and AZD1222.

Methods

This is a prospective cohort study in accordance with a template provided by the World Health Organization. The target population includes citizens of seven cities in Iran who have received one of the available COVID-19 vaccines according to the national instruction on vaccination. The participants are followed for three months after they receive the second dose of the vaccine. For each type of vaccine, 30,000 people will be enrolled in the study of whom the first 1,000 participants are in the reactogenicity subgroup. The reactogenicity outcomes will be followed seven days after vaccination. Any hospitalization, COVID-19 disease, or other minor outcomes will be investigated in weekly follow-ups. The data are gathered through self-reporting of participants in a mobile application or phone calls to them. The study outcomes may be investigated for the third and fourth doses of vaccines. Other long-term outcomes may also be investigated after the expansion of the follow-up period. We have planned to complete data collection for the current objectives by the end 2022.

Discussion

The results of this study will be published in different articles. A live dashboard is also available for managers and policymakers. All data will be available on reasonable requests from the corresponding author.The use of the good and comprehensive guidelines provided by WHO, along with the accurate implementation of the protocol and continuous monitoring of the staff performance are the main strengths of this study which may be very useful for policymaking about COVID-19 vaccination.
Primary hyperparathyroidism in Saudi Arabia revisited: a multi-centre observational study
Authors: Al-Saleh Yousef , AlSohaim Abdullah , AlAmoudi Reem , AlQarni Ali , Alenezi Raed , Mahdi Layla , Alzanbaqi Hend , Nawar Samah M. , AlHarbi Hibah , ALMulla Abdulrhman , Al Qahtani Maryam , Salih Salih Bin , Al Anazi Faisal , Saleh Najla , Saleh Seham , AlAklabi Ali , Sabico Shaun , Al-Daghri Nasser M.
Published: June 2022

Purpose

Primary hyperparathyroidism (PHPT) is a common cause of hypercalcemia and remains understudied within the Arabian population. The present study, the largest of its kind within the Gulf Cooperation Council (GCC) countries, aims to determine the demographics and clinical presentation of PHPT in Saudi Arabia.

Methods

In this multi-center retrospective study involving three tertiary hospitals in different geographic locations of Saudi Arabia namely, Riyadh, Al Ahsa and Jeddah, a total of 205 out of 243 confirmed PHPT cases aged 16 to 93 years old were included (N = 96 from Riyadh; N = 59 from Al Ahsa and N = 50 from Jeddah). Demographics, clinical manifestations and surgical outcomes were recorded as well as laboratory and radiologic investigations including serum parathyroid hormone (PTH), 25(OH)D, adjusted calcium, estimated glomerular filtration rate (eGFR) and nuclear scan outcome.

Results

PHPT cases appeared to increase over time when compared to other local studies published so far, with 12.8 cases per 100,000 hospital population. Females outnumber males (3:1) with 86% seen as out-patients. The average age was 59.8 ± 15.5 years. Abnormal PTH scan was seen in 171 patients (83.4%). Kidney stones was the most common renal manifestation (32 cases, 15.6%) and osteoporosis was the most common skeletal manifestation (67 cases, 32.7%). Al Ahsa had the highest prevalence of multiple comorbidities at 54% and the highest prevalence of obesity as a single comorbidity (17%) compared to other regions (p < 0.05). Jeddah recorded the highest prevalence of osteoporosis with bone and joint pains (30%) (p < 0.05).

Conclusion

Comparison of present data with previous local studies suggest an increasing trend in PHPT cases in Saudi Arabia. Regional variations in the clinical presentation of PHPT were observed and warrant further investigation.
Implications of regulator of G-protein signaling 5 expression in the pathogenesis of primary and secondary hyperparathyroidism
Authors: Li Xin , Lu Yao , Zhang Ling , Song Aiping , Zhang Honglei , Pang Bo , Liu Jun , Sun Xiaoliang , Ji Haoyang , Huang Linping , Yang Meng
Published: June 2022

Objective

To study the protein and mRNA expressions of regulator of G-protein signaling 5 (RGS5) in the pathogenesis of hyperparathyroidism.

Methods

The expression of RGS5 protein in 20 primary hyperparathyroidism (PHPT), 31 secondary hyperparathyroidism (SHPT), and 20 control cases were studied by immunohistochemistry (IHC). The expression of RGS5 mRNA in 15 PHPT, 102 SHPT, and 7 normal parathyroid tissue were measured by quantitative real-time PCR (qRT-PCR) method.

Results

The expressions of RGS5 in PHPT tissues were significantly higher than that in SHPT and normal parathyroid tissues (P < 0.05). While the differences in RGS5 protein expressions between SHPT and respective control samples were not statistically significant (P > 0.05). Likewise, the RGS5 mRNA expression in PHPT was significantly higher than that in SHPT (P < 0.05) and normal parathyroid (P < 0.05) samples. In a similar line, the differences in RGS5 gene expressions between SHPT and control tissues were not statistically significant (P > 0.05).

Conclusions

The characteristic RGS5 protein and mRNA levels in hyperparathyroidism might be helpful in discovering the pathomechanism of hyperparathyroidism and novel therapeutic targets as well.
Factors influencing medical students’ approaches to learning in Qatar
Authors: Qureshi Sheila S. , Larson Adam H. , Vishnumolakala Venkat R.
Published: June 2022

Background

This study investigated the relevance of the revised 2-factor study process questionnaire (R-SPQ-2F) for exploring medical students’ approaches to learning in Qatar and identify how factors like gender, age, educational attainment, and prior experience with health care influence students’ adoption of deep approaches to learning.

Methods

The sample consisted of 108 medical students (44% male, 56% female) from all four years of medical school at Weill Cornell Medicine-Qatar (WCM-Q). Participants completed the 20-item R-SPQ-2F questionnaire to measure their learning approaches through a structural model contrasting deep and surface learning. Participants also completed a survey collecting demographic information.

Results

Statistical analysis revealed significant differences in deep learning approaches across year levels for both men and women. Additionally, educational attainment played a significant role in students’ approaches to learning.

Conclusions

Based on structural equation modeling, this cross-verification study supports the R-SPQ-2F instrument and offers additional evidence for its robustness and application to medical education. These findings may help educational and program leaders in Qatar better understand medical students’ learning approaches to enhance their pedagogical practices.
Coping strategies adopted by medical residents in dealing with work-related stress: a mixed-methods study
Authors: Manzoor Shamaila , Sajjad Madiha , Anwar Idrees , Rafi Aisha
Published: June 2022

Background

This study was carried out to identify and explore the difference in coping strategies for dealing with stress; adopted by medical residents in surgical and nonsurgical specialties.

Methods

A mixed methods approach, was chosen for this study. In phase one (quantitative); data were collected by a web-based survey, using a structured questionnaire. This survey was carried out in five major teaching hospitals of Rawalpindi & Muzaffarabad in 2020. Purposive sampling was done and data were analysed using SPSS, recording frequencies and major trends. In phase two (qualitative); six focus group discussions were carried out with 24 participants, using semi-structured questions and prompts. Convenient sampling was done from the cohort of phase 1. These focus group discussions, explored the various coping strategies adopted by medical residents. Later, the data were analysed manually for development of codes, sub-themes and themes.

Results

Out of 250 (100%) participants, 146 (58%) participants responded to the online survey. Surgical residents had a higher response rate (60%, n = 87) than nonsurgical residents. Moreover, female participation (54%, n = 79) was greater than male participation (46%, n = 67). The Mann-Whitney U test was statistically significant only for seeking medical advice to cope with stress (P = .029). There was no statistically significant difference found between the coping strategies, employed by medical residents.

In focus group discussions, female involvement was more (58% n = 14) than their counterparts. Four main themes were developed after data analysis: self-regulation, tailor-made strategies, educational focus and support system. Finally, minor differences were obtained qualitatively; like, socializing is preferred by surgical residents whereas, spiritualism is chosen by nonsurgical residents.

Conclusion

Quantitatively, no significant differences were found between the coping strategies of medical residents, against work-related stress. However, minor differences were obtained qualitatively due to difference in job demands and level of burnout between these two specialities.
A unique self-truncation of bacterial GH5 endoglucanases leads to enhanced activity and thermostability
Authors: Wu Mei-Huey , Kao Mu-Rong , Li Chen-Wei , Yu Su-May , Ho Tuan-Hua David
Published: June 2022

Background

β-1,4-endoglucanase (EG) is one of the three types of cellulases used in cellulose saccharification during lignocellulosic biofuel/biomaterial production. GsCelA is an EG secreted by the thermophilic bacteriumGeobacillussp. 70PC53 isolated from rice straw compost in southern Taiwan. This enzyme belongs to glycoside hydrolase family 5 (GH5) with a TIM-barrel structure common among all members of this family. GsCelA exhibits excellent lignocellulolytic activity and thermostability. In the course of investigating the regulation of this enzyme, it was fortuitously discovered that GsCelA undergoes a novel self-truncation/activation process that appears to be common among GH5 enzymes.

Results

Three diverse Gram-positive bacterial GH5 EGs, but not a GH12 EG, undergo an unexpected self-truncation process by removing a part of their C-terminal region. This unique process has been studied in detail with GsCelA. The purified recombinant GsCelA was capable of removing a 53-amino-acid peptide from the C-terminus. Natural or engineered GsCelA truncated variants, with up to 60-amino-acid deletion from the C-terminus, exhibited higher specific activity and thermostability than the full-length enzyme. Interestingly, the C-terminal part that is removed in this self-truncation process is capable of binding to cellulosic substrates of EGs. The protein truncation, which is pH and temperature dependent, occurred between amino acids 315 and 316, but removal of these two amino acids did not stop the process. Furthermore, mutations of E142A and E231A, which are essential for EG activity, did not affect the protein self-truncation process. Conversely, two single amino acid substitution mutations affected the self-truncation activity without much impact on EG activities. InGeobacillussp. 70PC53, the full-length GsCelA was first synthesized in the cell but progressively transformed into the truncated form and eventually secreted. The GsCelA self-truncation was not affected by standard protease inhibitors, but could be suppressed by EDTA and EGTA and enhanced by certain divalent ions, such as Ca2+, Mg2+, and Cu2+.

Conclusions

This study reveals novel insights into the strategy of Gram-positive bacteria for directing their GH5 EGs to the substrate, and then releasing the catalytic part for enhanced activity via a spontaneous self-truncation process.
SRF: a seriously responsible factor in cardiac development and disease
Authors: Deshpande Anushka , Shetty Prithviraj Manohar Vijaya , Frey Norbert , Rangrez Ashraf Yusuf
Published: June 2022

The molecular mechanisms that regulate embryogenesis and cardiac development are calibrated by multiple signal transduction pathways within or between different cell lineages via autocrine or paracrine mechanisms of action. The heart is the first functional organ to form during development, which highlights the importance of this organ in later stages of growth. Knowledge of the regulatory mechanisms underlying cardiac development and adult cardiac homeostasis paves the way for discovering therapeutic possibilities for cardiac disease treatment. Serum response factor (SRF) is a major transcription factor that controls both embryonic and adult cardiac development. SRF expression is needed through the duration of development, from the first mesodermal cell in a developing embryo to the last cell damaged by infarction in the myocardium. Precise regulation of SRF expression is critical for mesoderm formation and cardiac crescent formation in the embryo, and altered SRF levels lead to cardiomyopathies in the adult heart, suggesting the vital role played by SRF in cardiac development and disease. This review provides a detailed overview of SRF and its partners in their various functions and discusses the future scope and possible therapeutic potential of SRF in the cardiovascular system.
Interleukin-20 is involved in dry eye disease and is a potential therapeutic target
Authors: Wang Hsiao-Hsuan , Chen Wei-Yu , Huang Yi-Hsun , Hsu Sheng-Min , Tsao Yeou-Ping , Hsu Yu-Hsiang , Chang Ming-Shi
Published: June 2022

Background

Dry eye disease (DED) is a common disease in ophthalmology, affecting millions of people worldwide. Recent studies have shown that inflammation is the core mechanism of DED. IL-20 is a proinflammatory cytokine involved in various inflammatory diseases. Therefore, we aimed to explore the role of this cytokine in the pathogenesis of DED and evaluate the therapeutic potential of the anti-IL-20 monoclonal antibody (mAb) 7E for DED treatment.

Methods

Clinical tear samples from patients with DED and non-DED controls were collected and their IL-20 protein levels were determined. We established three DED animal models to explore the role of IL-20 and the efficacy of IL-20 antibody in DED. Benzalkonium chloride (BAC)-induced over-evaporative DED, extra-orbital lacrimal gland excision (LGE)-induced aqueous tear-deficient DED, and desiccating stress (DS)-induced combined over-evaporative and aqueous tear-deficient DED animal models were established to investigate the role of IL-20. The anti-IL-20 antibody 7E was established to neutralize IL-20 activity. The effects of IL-20 or 7E on human corneal epithelial cells and macrophages under hyperosmotic stress were analyzed. 7E was topically applied to eyes to evaluate the therapeutic effects in the DED animal models.

Results

IL-20 was significantly upregulated in the tears of patients with DED and in the tears and corneas of DED animal models. Under hyperosmotic stress, IL-20 expression was induced via NFAT5 activation in corneal epithelial cells. 7E suppressed hyperosmotic stress-induced activation of macrophages. IL-20 induced cell death in corneal epithelial cells and 7E protected cells from hyperosmotic stress-induced cell death. Blocking IL-20 signaling with 7E protected mice from BAC-induced, LGE-induced, and DS-induced DED by reducing DED symptoms and inhibiting inflammatory responses, macrophage infiltration, apoptosis, and Th17 populations in the conjunctiva and draining lymph nodes.

Conclusions

Our results demonstrated the functions of IL-20 in DED and presented a potential therapeutic option for this condition.

Graphical Abstract
Serum antioxidant vitamins and respiratory morbidity and mortality: a pooled analysis
Authors: Salo Paivi M. , Mendy Angelico , Wilkerson Jesse , Molsberry Samantha A. , Feinstein Lydia , London Stephanie J. , Fessler Michael B. , Thorne Peter S. , Zeldin Darryl C.
Published: June 2022

Background

Oxidative stress plays a key role in the pathogenesis of respiratory diseases; however, studies on antioxidant vitamins and respiratory outcomes have been conflicting. We evaluated whether lower serum levels of vitamins A, C, D, and E are associated with respiratory morbidity and mortality in the U.S. adult population.

Methods

We conducted a pooled analysis of data from the 1988–1994 and 1999–2006 National Health and Nutrition Examination Survey (participants aged ≥ 20 years). We estimated covariate-adjusted odds ratios (aOR) per interquartile decrease in each serum vitamin level to quantify associations with respiratory morbidity, and covariate-adjusted hazard ratios (aHR) to quantify associations with respiratory mortality assessed prospectively through 2015. Vitamin supplementation and smoking were evaluated as potential effect modifiers.

Results

Lower serum vitamin C increased the odds of wheeze among all participants (overall aOR: 1.08, 95% CI: 1.01–1.16). Among smokers, lower serum α-tocopherol vitamin E increased the odds of wheeze (aOR: 1.11, 95% CI: 1.04–1.19) and chronic bronchitis/emphysema (aOR: 1.13, 95% CI: 1.03–1.24). Conversely, lower serum γ-tocopherol vitamin E was associated with lower odds of wheeze and chronic bronchitis/emphysema (overall aORs: 0.85, 95% CI: 0.79–0.92 and 0.85, 95% CI: 0.76–0.95, respectively). Lower serum vitamin C was associated with increased chronic lower respiratory disease (CLRD) mortality in all participants (overall aHR: 1.27, 95% CI: 1.07–1.51), whereas lower serum 25-hydroxyvitamin D (25-OHD) tended to increase mortality from CLRD and influenza/pneumonia among smokers (aHR range: 1.33–1.75). Mortality from influenza/ pneumonia increased with decreasing serum vitamin A levels in all participants (overall aHR: 1.21, 95% CI: 0.99–1.48). In pooled analysis, vitamin C deficiency and 25-OHD insufficiency were associated with mortality from influenza/pneumonia, increasing mortality risk up to twofold.

Conclusions

Our analysis of nationally representative data on over 34,000 participants showed that lower serum levels of vitamins A, C, D, and α-tocopherol vitamin E are associated with increased respiratory morbidity and/or mortality in U.S. adults. The results underscore the importance of antioxidant vitamins in respiratory health.
Low total osteocalcin levels are associated with all-cause and cardiovascular mortality among patients with type 2 diabetes: a real-world study
Authors: Shen Yun , Chen Lei , Zhou Jian , Wang Chunfang , Gao Fei , Zhu Wei , Hu Gang , Ma Xiaojing , Xia Han , Bao Yuqian
Published: June 2022

Background

The association between osteocalcin and mortality has been scantly studied. We aimed to investigate the association between osteocalcin along with its trajectories and mortality based on long-term longitudinal data.

Methods

We performed a retrospective cohort study of 9413 type 2 diabetic patients with at least three measurements of total serum osteocalcin within 3 years since their first inpatient diagnosis of type 2 diabetes. Baseline, mean values of osteocalcin levels and their trajectories were used as exposures. A multivariable-adjusted Cox proportional hazards model was used to estimate the association of osteocalcin levels and their trajectories with mortality.

Results

During a mean follow-up of 5.37 years, 1638 patients died, of whom 588 were due to cardiovascular events. Multivariable-adjusted hazard ratios (HRs) across quintiles of baseline osteocalcin levels were 2.88 (95% confidence interval (CI) 2.42–3.42), 1.65 (95% CI 1.37–1.99), 1.17 (95% CI 0.96–1.42), 1.00, and 1.92 (95% CI 1.60–2.30) for all-cause mortality, and 3.52 (95% CI 2.63–4.71), 2.00 (95% CI 1.46–2.73), 1.03 (95% CI 0.72–1.47), 1.00, 1.67 (95% CI 1.21–2.31) for CVD mortality, respectively. When we used the mean values of osteocalcin as the exposure, U-shaped associations were also found. These U-shaped associations were consistent among patients of different baseline characteristics. Patients with a stable or even increasing trajectory of osteocalcin may have a lower risk of both all-cause and CVD mortality.

Conclusions

A U-shape association between baseline osteocalcin and mortality was observed among patients with type 2 diabetes. Patients with lower levels of serum osteocalcin during follow-ups had higher risks for all-cause and cardiovascular mortality.
Laparoscopic hepatopancreaticoduodenectomy for synchronous gallbladder cancer and extrahepatic cholangiocarcinoma: a case report
Authors: Yao Guo-Liang
Published: June 2022

Background

Hepatopancreaticoduodenectomy (HPD) is one of the most complex procedures, and it is very rarely reported. Laparoscopic HPD (LHPD) is even rarer. To date, there are only 3 reports of LHPD for locally advanced gallbladder cancer (GBC) or extrahepatic cholangiocarcinoma (ECC). This is the first report of LHPD for synchronous GBC and ECC.

Case presentation

A 75-year-old female patient complained of jaundice for 2 weeks without fever or abdominal pain. She was diagnosed with synchronous GBC and ECC. After a comprehensive preparation, she underwent a laparoscopic pancreaticoduodenectomy and resection of hepatic segments of IVb and V, and her digestive tract reconstruction followed Child’s methods. She was discharged on the 12th day postoperatively without pancreatic leakage, biliary leakage, or liver failure.

Conclusions

LHPD is safe and feasible for selected cases of GBCs or ECCs.
The impact of intraoperative radiotherapy on breast cancer: focus on the levels of angiogenic factors
Authors: Nafissi Nahid , Mohammadlou Maryam , Akbari Mohammad Esmaeil , Mahdavi Seyed Rabie , Sheikh Maryam , Borji Mohammad , Babaee Ebrahim , Baharlou Rasoul
Published: June 2022

Objective

Angiogenesis is one of the hallmarks of cancers that is involved in tumor progression. Angiogenic factors induce the formation of new blood vessels and tumor extension, and finally reduce the survival of patients. Intraoperative radiotherapy (IORT), in which radiation is delivered to the tumor bed can kill cells and change tumor microenvironment. Here, we compared the impact of IORT on the levels of angiogenic factors in the blood and surgical wound fluids (SWF) of the breast cancer patients.

Patients and methods

Three hundred sixty patients, who had undergone breast-conserving surgery between 2013 and 2018, were enrolled in IORT and non-IORT groups non-randomly. Blood and drained wound fluid (WF) samples were collected from the patients before and after surgery, followed by quantification of the amounts of TGF-β, EGF, FGF, VEGF, and DLL4 in the patients using ELISA.

Results

Our results were indicative of significant differences between the pre-surgery and post-surgery serum levels of EGF, DLL4, and VEGF. Furthermore, ROC analyses showed that TGF-β and DLL4 can differentiate of the early-stage from late-stage of the disease. Interestingly, the rate of the death and recurrence was reduced in IORT group.

Conclusions

In summary, IORT is a safe and effective treatment that can affect angiogenic factors and improve the overall- and recurrence-free survival of breast cancer patients.
Australian guideline on management of diabetes‐related foot infection: part of the 2021 Australian evidence‐based guidelines for diabetes‐related foot disease
Authors: Commons Robert J. , Charles James , Cheney Jane , Lynar Sarah A. , Malone Matthew , Raby Edward ,   Australian Diabetes‐related Foot Disease Guidelines & Pathways Project
Published: June 2022

Background

Diabetes‐related foot infections cause substantial morbidity and mortality, both globally and in Australia. There is a need for up‐to‐date evidence‐based guidelines to ensure optimal management of patients with diabetes‐related foot infections. We aimed to identify and adapt high quality international guidelines to the Australian context to become the new Australian evidence‐based guideline for people with a diabetes‐related foot infection.

Methods

Following Australian National Health and Medical Research Council (NHMRC) procedures we identified the 2019 International Working Group on the Diabetic Foot (IWGDF) guidelines as suitable for adaptation to the Australian context. Guidelines were screened, assessed and judged by an expert panel for the Australian context using the guideline adaptation frameworks ADAPTE and Grading of Recommendations Assessment, Development and Evaluation (GRADE). Judgements led to recommendations being adopted, adapted or excluded, with additional consideration regarding their implementation, monitoring and future research for the Australian context. Clinical pathways were then developed to assist implementation.

Results

Of 36 original diabetes‐related foot infection IWGDF sub‐recommendations, 31 were adopted, four were adapted and one was excluded. Adaption was primarily undertaken due to differences or clarification of the sub‐recommendations' intended population. One sub‐recommendation was excluded due to substantial differences in judgements between the panel and IWGDF and unacceptable heterogeneity of the target population. Therefore, we developed 35 evidence‐based sub‐recommendations for the Australian context that should guide best practice diagnosis and management of people with diabetes‐related foot infection in Australia. Additionally, we incorporated these sub‐recommendations into two clinical pathways to assist Australian health professionals to implement these evidence‐based sub‐recommendations into clinical practice. The six guidelines and the full protocol can be found at: https://www.diabetesfeetaustralia.org/new‐guidelines/.

Conclusions

A new national guideline for the diagnosis and management of people with diabetes‐related foot infections were successfully developed for the Australian context. In combination with simplified clinical pathway tools they provide an evidence‐based framework to ensure best management of individuals with diabetes‐related foot infections across Australia and highlight considerations for implementation and monitoring.
Evaluation of short-term epigenetic age fluctuation
Authors: Komaki Shohei , Ohmomo Hideki , Hachiya Tsuyoshi , Sutoh Yoichi , Ono Kanako , Furukawa Ryohei , Umekage So , Otsuka-Yamasaki Yayoi , Minabe Shiori , Takashima Akira , Tanno Kozo , Sasaki Makoto , Shimizu Atsushi
Published: June 2022

Considerable effort has been spent on lowering and maintaining the epigenetic age. However, the extent to which epigenetic age fluctuates under normal conditions is poorly understood. Therefore, we analyzed methylation data from monocytes and peripheral blood mononuclear cells collected from two Japanese men. The ranges of the Pan-tissue, Skin and blood, and DNAm PhenoAge epigenetic age during 3 months were ≥ 5.62, ≥ 3.04, and ≥ 8.23 years, and the maximum daily changes were 5.21, 3.20, and 6.53 years, respectively. These fluctuations were not suppressed by correcting for cell-type composition. Although the underlying biological mechanism remains unclear, there was a nonnegligible degree of age fluctuation which should inform personalized clinical applications.
A comparison of mixed-variables Bayesian optimization approaches
Authors: Cuesta Ramirez Jhouben , Le Riche Rodolphe , Roustant Olivier , Perrin Guillaume , Durantin Cédric , Glière Alain
Published: June 2022

Most real optimization problems are defined over a mixed search space where the variables are both discrete and continuous. In engineering applications, the objective function is typically calculated with a numerically costly black-box simulation. General mixed and costly optimization problems are therefore of a great practical interest, yet their resolution remains in a large part an open scientific question. In this article, costly mixed problems are approached through Gaussian processes where the discrete variables are relaxed into continuous latent variables. The continuous space is more easily harvested by classical Bayesian optimization techniques than a mixed space would. Discrete variables are recovered either subsequently to the continuous optimization, or simultaneously with an additional continuous-discrete compatibility constraint that is handled with augmented Lagrangians. Several possible implementations of such Bayesian mixed optimizers are compared. In particular, the reformulation of the problem with continuous latent variables is put in competition with searches working directly in the mixed space. Among the algorithms involving latent variables and an augmented Lagrangian, a particular attention is devoted to the Lagrange multipliers for which a local and a global estimation techniques are studied. The comparisons are based on the repeated optimization of three analytical functions and a beam design problem.
The frailty, outcomes, recovery and care steps of critically ill patients (FORECAST) study: pilot study results
Authors: Muscedere John , Bagshaw Sean M. , Boyd Gordon , Sibley Stephanie , Norman Patrick , Day Andrew , Hunt Miranda , Rolfson Darryl
Published: June 2022

Introduction

Frailty is common in critically ill patients and is associated with increased morbidity and mortality. There remains uncertainty as to the optimal method/timing of frailty assessment and the impact of care processes and adverse events on outcomes is unknown. We conducted a pilot study to inform on the conduct, design and feasibility of a multicenter study measuring frailty longitudinally during critical illness, care processes, occurrence of adverse events, and resultant outcomes.

Methods

Single-center pilot study enrolling patients over the age of 55 admitted to an Intensive Care Unit (ICU) for life-support interventions including mechanical ventilation, vasopressor therapy and/or renal replacement therapy. Frailty was measured on ICU admission and hospital discharge with the Clinical Frailty Scale (CFS), the Frailty Index (FI) and CFS at 6-month follow-up. Frailty was defined as CFS ≥ 5 and a FI ≥ 0.20. Processes of care and adverse events were measured during their ICU and hospital stay including nutritional support, mobility, nosocomial infections and delirium. ICU, hospital and 6 months were determined.

Results

In 49 patients enrolled, the mean (SD) age was 68.7 ± 7.9 with a 6-month mortality of 29%. Enrollment was 1 patient/per week. Frailty was successfully measured at different time points during the patients stay/follow-up and varied by method/timing of assessment; by CFS and FI, respectively, in 17/49 (36%), 23/49 (47%) on admission, 22/33 (67%), 21/33 (63%) on hospital discharge and 11/30 (37%) had a CFS ≥ 5 at 6 months. Processes of care and adverse events were readily captured during the ICU and ward stay with the exception of ward nutritional data. ICU, hospital outcomes and follow-up outcomes were worse in those who were frail irrespective of ascertainment method. Pre-existing frailty remained static in survivors, but progressed in non-frail survivors.

Discussion

In this pilot study, we demonstrate that frailty measurement in critically ill patients over the course and recovery of their illness is feasible, that processes of care and adverse events are readily captured, have developed the tools and obtained data necessary for the planning and conduct of a large multicenter trial studying the interaction between frailty and critical illness.
Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice
Authors: Du Lu , Peng Guang-Hua
Published: June 2022

Background

It has been found that the extensive use of anticancer drugs containing DNA-alkylating agents not only target cancer cells but also cause retinal inflammation through toxic intermediates. Complement C3 (C3) is a core component of the complement activation pathway, and dysregulation of the complement pathway is involved in several retinal degenerative diseases. However, whether C3 plays a critical role in alkylation-induced retinal degeneration is unclear.

Methods

Following treatment with the alkylating agent methyl methane sulfonate (MMS), the C3 mRNA and protein level was measured, DNA damage and photoreceptor cell death were assessed in both wild-type (WT) C57BL/6J and C3 knockout (KO) mice.

Results

We determined that complement pathway is activated following MMS treatment, and C3 knockout (KO) increased the rate of photoreceptor cell survival and preserved visual function. The mRNA levels of nuclear erythroid-related factor 2 (Nrf2) and related genes were higher after MMS application in C3 KO mice.

Conclusion

In summary, our study found that C3 KO promotes photoreceptor cell survival and activates the Nrf2 signaling pathway in the context of alkylation-induced retinal degeneration.
A theory of very short-time price change: security price drivers in times of high-frequency trading
Authors: Virgilio Gianluca P. M.
Published: June 2022

Academic research has identified several factors that affect price movements; however, the scenario changes abruptly in the case of very short time price changes (VSTPC). This topic is not specifically examined in the existing literature; nonetheless, the behavior of the market microstructure is quite different at the subsecond scale. Indeed, below a certain psychological time threshold, most factors typically influencing price changes cease to apply. This paper analyzes several parameters considered to affect price changes and identifies four of them as potentially influencing VSTPC. These factors are previous volatility, scarce liquidity, high quantity exchanged, and stop-loss (SL) orders (seldom mentioned in the literature). These four parameters are examined by means of a mathematical model, audit trail data analysis, Granger-causality testing, and agent-based model. The results of these four techniques converge to suggest a nonlinear combination of previous volatility, liquidity, and SL orders as the main causes of excess volatility. However, contrary to mainstream literature on trading time above a certain psychological threshold, the volumes exchanged are not integral agents for VSTPC. Currently, financial markets face many ultrafast orders, yet a coherent theory of price change at time scales incomprehensible by humans and only manageable by computers is still lacking. The theory presented in this paper attempts to fill this gap. The outcome of such a theory is important for purposes of market stability, crisis avoidance, investment planning, risk management, and high-frequency trading.
Electroencephalogram evaluation of accidental cerebral congestion during unexpected superior vena cava clamping: a case report
Authors: Miyoshi Hirotsugu , Nakamura Ryuji , Otsuki Sachiko , Noda Yuko , Saeki Noboru , Tsutsumi Yasuo M.
Published: June 2022

Background

Intraoperative superior vena cava (SVC) clamping causes hypotension and cerebral congestion. There is no established method for monitoring brain function during cerebral congestion. We encountered a case of cerebral congestion caused by unexpected SVC clamping.

Case presentation

A 64-year-old man underwent SVC clamping during lung tumor resection. The entropy and electroencephalogram monitoring values decreased with SVC clamping and increased in response to the release of congestion by phlebotomy and SVC declamping.

Conclusions

Because entropy sharply reflects brain viability during cerebral congestion, it was considered helpful in evaluation of the monitoring of cerebral congestion.
Toward social neuropsychology of epilepsy: a meta-analysis on social cognition in epilepsy phenotypes and a critical narrative review on assessment methods
Authors: Eicher Marcel , Jokeit Hennric
Published: June 2022

Background

The aim of this review is to (a) characterize social cognition impairments in the domains of emotion recognition (ER) and theory of mind (ToM) in patients with epilepsy and (b) to review assessment tools with a focus on their validity and usability in clinical practice.

Methods

An electronic search for clinical studies investigating social cognition in epilepsy populations vs healthy control subjects (HC) yielded 53 studies for the meta-analysis and descriptive review.

Results

Results suggest that (1) social cognition is significantly impaired in patients with temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE) and patients with epilepsy not originating within the temporal or frontal lobes including idiopathic generalized epilepsies (eTLE/eFLE); (2) there is no significant difference between eTLE/eFLE and TLE regarding ER, while TLE and FLE patients perform worse than those with eTLE/eFLE, without significant differences between FLE and TLE regarding ToM ability. A descriptive analysis of the most commonly used assessment tools and stimulus material in this field revealed a lack of ecological validity, usability, and economic viability for everyday clinical practice.

Conclusions

Our meta-analysis shows that patients with epilepsy are at a significantly increased risk of deficits in social cognition. However, the underlying multifactorial mechanisms remain unclear. Future research should therefore specifically address the impairment of processing and methodological problems of testing.
Behaviours that challenge in adults with intellectual disability: overview of assessment and management
Authors: Hassiotis Angela , Rudra Sonya
Published: June 2022

Up to a fifth of people with intellectual disabilities display challenging behaviour that has a significant impact on their health and quality of life. Psychotropic medication does not appear to confer any clinical benefits beyond risk reduction in acute situations. However, very few non-pharmacological treatments have clear evidence of clinical and cost-effectiveness and there is therefore often a dearth of advice as to which components or interventions would be helpful. To our knowledge no single model has been developed to provide a clear path from understanding the behaviour to the implementation of a therapeutic approach for such a complex clinical problem. In this article we describe a stepped-care model that needs to be further operationalised in the assessment and management of behaviours that challenge in adults with intellectual disabilities.
Suicide among users of mental health and addiction services in the first 10 months of the COVID-19 pandemic: observational study using national registry data
Authors: Walby Fredrik A. , Myhre Martin Ø. , Mehlum Lars
Published: June 2022

Although many studies have reported no rise in suicides in the general population following the COVID-19 pandemic, little is known regarding mental health and substance misuse service patients, groups who have reportedly faced substantial reductions in their access to care during phases of lockdown. However, in this observational study using national registry data, during the first 10 months of the pandemic we found no evidence of an increased risk among people in recent (within 12 months) contact with secondary care. Both long-term and differential effects on subgroups remain to be studied.
Functional Definition of Thyroid Hormone Response Elements Based on a Synthetic STARR-seq Screen
Authors: Flamant Frédéric , Zekri Yanis , Guyot Romain
Published: June 2022

When bound to thyroid hormone, the nuclear receptor TRα1 activates the transcription of a number of genes in many cell types. It mainly acts by binding DNA as a heterodimer with retinoid X receptors at specific response elements related to the DR4 consensus sequence. However, the number of DR4-like elements in the genome exceed by far the number of occupied sites, indicating that minor variations in nucleotides composition deeply influence the DNA-binding capacity and transactivation activity of TRα1. An improved protocol of synthetic self-transcribing active regulatory region sequencing was used to quantitatively assess the transcriptional activity of thousands of synthetic sites in parallel. This functional screen highlights a strong correlation between the affinity of the heterodimers for DNA and their capacity to mediate the thyroid hormone response.
Mechanosensitive Steroid Hormone Signaling and Cell Fate
Authors: Northey Jason J , Weaver Valerie M
Published: June 2022

Mechanical forces collaborate across length scales to coordinate cell fate during development and the dynamic homeostasis of adult tissues. Similarly, steroid hormones interact with their nuclear and nonnuclear receptors to regulate diverse physiological processes necessary for the appropriate development and function of complex multicellular tissues. Aberrant steroid hormone action is associated with tumors originating in hormone-sensitive tissues and its disruption forms the basis of several therapeutic interventions. Prolonged perturbations to mechanical forces may further foster tumor initiation and the evolution of aggressive metastatic disease. Recent evidence suggests that steroid hormone and mechanical signaling intersect to direct cell fate during development and tumor progression. Potential mechanosensitive steroid hormone signaling pathways along with their molecular effectors will be discussed in this context.
Atypical Alzheimer Disease Variants
Authors: Polsinelli Angelina J. , Apostolova Liana G.
Published: June 2022

PURPOSE OF REVIEW

This article discusses the clinical, neuroimaging, and biomarker profiles of sporadic atypical Alzheimer disease (AD) variants, including early-onset AD, posterior cortical atrophy, logopenic variant primary progressive aphasia, dysexecutive variant and behavioral variant AD, and corticobasal syndrome.

RECENT FINDINGS

Significant advances are being made in the recognition and characterization of the syndromically diverse AD variants. These variants are identified by the predominant cognitive and clinical features: early-onset amnestic syndrome, aphasia, visuospatial impairments, dysexecutive and behavioral disturbance, or motor symptoms. Although understanding of regional susceptibility to disease remains in its infancy, visualizing amyloid and tau pathology in vivo and CSF examination of amyloid-β and tau proteins are particularly useful in atypical AD, which can be otherwise prone to misdiagnosis. Large-scale research efforts, such as LEADS (the Longitudinal Early-Onset Alzheimer Disease Study), are currently ongoing and will continue to shed light on our understanding of these diverse presentations.

Understanding the clinical, neuroimaging, and biomarker profiles of the heterogeneous group of atypical AD syndromes improves diagnostic accuracy in patients who are at increased risk of misdiagnosis. Earlier accurate identification facilitates access to important interventions, social services and disability assistance, and crucial patient and family education.