bluuebunny/crossref_metadata_2025 huggingface dataset:
Under family control: The trend of sole candidate elections in Indonesia
Authors: Yakub Andi , Armunanto Andi Ali , Haryanto
Published: August 2022

The rise of sole candidates in various local head elections in Indonesia has been the subject of many scholarly critical analyses. Most of the analyses perceive the phenomenon as a symptom of incumbency advantages, weak electoral systems, and poor institutionalization of political parties. This article proposes a new argument with the family-based elite perspective controlling the sole candidates’ emergence process. We compared two regions in South Sulawesi province, explaining the political family networks that dominate the political competition by limiting candidature. The sole candidate elections can be understood by looking at family-based elite networks scattered in business networks, bureaucracy, political parties, aristocrats, and grassroots mass organizations. The families use an oligarchic elite network at the national level or a plural elite network at the grassroots level. The two types of family institutions are centralized and dispersed structures: Makassar has an oligarchy, while Gowa has relatively equal elite power. The family network’s power has closed or hijacked the electoral political competition, establishing control over local elections by creating monopolistic political networks. Political family control is essential in understanding the rise of sole candidate elections in political practices.
Factors influencing stress during the second imposed of COVID-19 social restrictions in Indonesia
Authors: Sulistyawati Sulistyawati , Aji Budi , Rokhmayanti Rokhmayanti , Wijayanti Siwi Pramatama Mars
Published: August 2022

Background:

The spread of the COVID-19 virus has had a significant impact on the governmental and social aspects, as well as to the psychological status of the population. In Indonesia, social restriction was a strategy to limit people’s mobility to reduce virus transmission. As social beings, the imposition of social restriction makes them fall into stress due to feeling lonely, and some cannot earn money. The aim of the study was to assess the factor association of stress level and resilience of the Indonesian people during the imposition of the second social restriction due to the COVID-19 pandemic.

Design and method:

A cross-sectional study was performed on respondents aged at least 18 years on 29 July–16 August 2021, when the social restriction was enforced for the second time. The online survey was conducted through several social media platforms (Facebook, Instagram, Twitter, and WhatsApp) to 256 respondents. The analysis was carried out descriptively and analytically using the chi-square and binary logistic regression.

Results:

This study shows that there is a significant relationship between age ( p < 0.001), marital status ( p < 0.001), occupation ( p < 0.001), income before and during the pandemic ( p < 0.001) and resilience level to stress level among Indonesian. Resilience level is the only protective factor for people to not get stressed. Being normal resilience put them at 0.05 times (95% CI 0.01–0.76) more likely to have low perceived stress than low resilience.

Conclusion:

Resilience level is the only factor that influence stress level among people in Indonesia during the second imposed social restriction in Indonesia.
An Examination of Utilization Rates Over Time of Nerve and Tendon Transfers in Canada to Improve Upper Limb Function in Cervical Spinal Cord Injury
Authors: Dengler Jana , Perlman Maytal , Jennett Michelle , Marcon Edyta , Guilcher Sara
Published: August 2022

Introduction: Upper limb function loss in cervical spinal cord injury (SCI) contributes to substantial disability, and negatively impacts quality of life. Nerve transfer and tendon transfer surgery can provide improved upper limb function. This study assessed the utilization of nerve and tendon transfer surgery for individuals with tetraplegia in Canada. Methods: Data from the Canadian Institute for Health Information's Discharge Abstracts Database and the National Ambulatory Care Reporting System were used to identify the nerve and tendon transfer procedures performed in individuals with tetraplegia (2004-2020). Cases were identified using cervical SCI ICD-10-CA codes and Canadian Classification of Intervention codes for upper extremity nerve and tendon transfers. Data on sex, age at time of procedure, province, and hospital stay duration were recorded. Results: From 2004 to 2020, there were ≤80 nerve transfer procedures (81% male, mean age 38.3 years) and 61 tendon transfer procedures (78% male, mean age 45.0 years) performed (highest in Ontario and British Columbia). Using an estimate of 50% eligibility, an average of 1.3% of individuals underwent nerve transfer and 1.0% underwent tendon transfer. Nerve transfers increased over time (2004-2009, n = <5; 2010-2015, n = 27; 2016-2019, n = 49) and tendon transfers remained relatively constant. Both transfer types were performed as day-surgery or single night stay. Conclusions: Nerve and tendon transfer surgery to improve upper limb function in Canadians with tetraplegia remains low. This study highlights a substantial gap in care for this vulnerable population. Identification of barriers that prevent access to care is required to promote best practice for upper extremity care.
Management of Intracranial Sinusitis Complications in Children and Adolescents: Similarities and Differences Among Otolaryngology Subspecialists
Authors: Adil Eelam , Kim Jamie J. , Kawai Kosuke , Cunningham Michael J.
Published: August 2022

The purpose of this study was to compare the management of intracranial sinusitis complications in pediatric patients between members of the American Rhinologic Society (ARS) and the American Society of Pediatric Otolaryngology (ASPO). A cross‐sectional web‐based survey was distributed twice to the ASPO and ARS membership over an 8‐month period. The overall survey response rate was 12.1% (7.5% of ARS members and 17.3% of ASPO members). Recommended management was similar with respect to the use of intravenous antibiotics, nasal saline irrigations, topical decongestants, and nasal steroid sprays. Recommendations diverged with regards to systemic steroid use and urgent/emergent endoscopic sinus surgery (ESS). ARS members were more likely to recommend systemic corticosteroids. ASPO members were more likely to recommend immediate ESS. Based on survey responses, we found differences in practice patterns among subspecialists, which indicates additional collaborative research between societies is necessary to develop and disseminate evidence‐based guidelines for these patients.

Level of Evidence: 4
Analysis of ocean ontologies in three frameworks: A study of law of the sea discourse
Authors: Burns Vanessa
Published: August 2022

Legal frameworks have historically used a colonial territorialist approach to governing ocean space. The United Nations Convention on the Law of the Sea (1982) represents a theoretical departure from colonial territorialism. Instead, UNCLOS employs a functionalist logic approach that is based on principles of sovereignty and consent and uses administrative reasoning as a basis for decision-making. This paper investigates what ontological principles are employed in the development of UNCLOS and asks how these are reproduced in other frameworks. I consider whether ontologies can be extrapolated and studied as latent but agential positions in ocean law and governance frameworks and examine how they might be obstructive to the development of effective regional ocean governance. Lastly, I ask whether ontological principles can be reformed, and through what type of interventions this might be achieved. Results show that tenets of colonial territorialism persist in UNCLOS as terrestrialising practices that are reappropriated towards marine communities. Further, that there are fundamental ways in which ontological principles are obstructive to conservation goals in ocean governance frameworks. Lastly, while the structural reproduction of ontological principles between frameworks resists intervention, evidence suggests that interventionist legal mechanisms that displace anthropocentrisms may offer distinct opportunities for reform.
Improving health literacy with mumps, measles and rubella (MMR) vaccination: comparison of the readability of MMR patient-facing literature and MMR scientific abstracts
Authors: Downey Tina , Millar Beverley C. , Moore John E.
Published: August 2022

Background:

Historically, there have been many factors that have influenced mumps, measles and rubella (MMR) vaccine uptake, including media bias, social/economic determinants, parental education level, deprivation and concerns over vaccine safety. Readability metrics through online tools are now emerging as a means for healthcare professionals to determine the readability of patient-facing vaccine information. The aim of this study was to examine the readability of patient-facing materials describing MMR vaccination, through employment of nine readability and text parameter metrics, and to compare these with MMR vaccination literature for healthcare professionals and scientific abstracts relating to MMR vaccination.

Materials and methods:

The subscription-based online Readable program (readable.com) was used to determine nine readability indices using various readability formulae: Established readability metrics ( n = 5) (Flesch–Kinkaid Grade Level, Gunning Fog Index, SMOG Index, Flesch Reading Ease and New Dale-Chall Score), as well as Text parameters ( n = 4) (sentence count, word count, number of words per sentence, number of syllables per word) with 47 MMR vaccination texts [patient-facing literature ( n = 22); healthcare professional–focused literature ( n = 8); scientific abstracts ( n = 17)].

Results:

Patient-facing vaccination literature had a Flesch Reading Ease score of 58.4 and a Flesch–Kincaid Grade Level of 8.1, in comparison with poorer readability scores for healthcare professional literature of 30.7 and 12.6, respectively. MMR scientific abstracts had the poorest readability (24.0 and 14.8, respectively). Sentence structure was also considered, where better readability metrics were correlated with significantly lower number of words per sentence and less syllables per word.

Conclusion:

Use of these readability tools enables the author to ensure their research is more readable to the lay audience. Patient co-production initiatives would help to ensure that not only can the target audience read the literature, but that they understand the content. Increased patient-centric focus groups would give better insights into reasons for MMR-associated vaccine hesitation and vaccine refusal.
The effect of disease onset chronology on mortality among patients with multimorbidity: A Danish nationwide register study
Authors: Willadsen Tora G , Siersma Volkert , Nicolaisdóttir Dagny R , Køster-Rasmussen Rasmus , Reventlow Susanne , Rozing Maarten
Published: August 2022

Background

Multimorbidity is associated with increased mortality. Certain combinations of diseases are known to be more lethal than others, but the limited knowledge of how the chronology in which diseases develop impacts mortality may impair the development of effective clinical interventions for patients with multimorbidity.

Objective

To explore if in multimorbidity the chronology of disease onset is associated with mortality. Design: A prospective nationwide cohort study, including 3,986,209 people aged ≥18 years on 1 January 2000, was performed. We included ten diagnosis groups: lung, musculoskeletal, endocrine, mental, cancer, neurological, gastrointestinal, cardiovascular, kidney, and sensory organs. We defined multimorbidity as the presence of at least two diagnoses from two diagnosis groups (out of ten). To determine mortality, logistic regression models were used to calculate odds ratios (OR) and ratio of ORs (RORs).

Results

For most combinations of multimorbidity, the chronology of disease onset does not change mortality. However, when multimorbidity included mental health diagnoses, mortality was in general higher if the mental health diagnosis appeared first. If multimorbidity included heart and sensory diagnoses, mortality was higher if these developed second. For the majority of multimorbidity combinations, there was excess mortality if multimorbidity was diagnosed simultaneously, rather than consecutively, for example, heart and kidney (3.58 ROR; CI 2.39–5.36), or mental health and musculoskeletal diagnoses (2.38 ROR; CI 1.70–3.32).

Conclusions

Overall, in multimorbidity, the chronology in which diseases develop is not associated with mortality, with few exceptions. For almost all combinations of multimorbidity, diagnoses act synergistically in relation to mortality if diagnosed simultaneously.
Behavioral Strategies for Trauma-Informed Elementary General Music Education for Students With Emotional/Behavioral Disorders: A Review of the Literature
Authors: Price Erin E.
Published: August 2022

Elementary general music teachers encounter challenging behaviors in the music classroom when teaching students with emotional/behavioral disorders (EBD), which require prevention and response. In this article, I reviewed literature on pedagogical strategies and interventions for students with EBD in the elementary general music classroom. The review is organized as follows: (a) introduction and process, (b) overview of trauma, (c) overview of EBD, (d) principles of trauma-informed care, and (e) summary and recommendations. Through this review, I present current knowledge on best practices for understanding and framing the unique behavioral needs of special learners with EBD through a trauma-informed lens.
Hypothalamic orexinergic neurons modulate pain and itch in an opposite way: pain relief and itch exacerbation
Authors: Kaneko Tatsuroh , Kuwaki Tomoyuki , Kashiwadani Hideki
Published: August 2022

Pain and itch are recognized as antagonistic sensations; pain suppresses itch and inhibition of pain generates itch. There is still a lack of evidence about the neural mechanism of the interaction between pain and itch in the central nervous system. In this study, we focused on the orexin (ORX) neurons in the lateral hypothalamus (LH), which mediate various “defense responses” when animals confront stressors. We found that the scratching behaviors induced by the pruritogen were significantly suppressed in ORX-neuron-ablated (ORX-abl) mice. The exaggerated pain behavior and attenuated itch behavior observed in ORX-abl mice indicated that ORX neurons modulate pain and itch in an opposite way, i.e., pain relief and itch exacerbation. In addition, most of the ORX neurons responded to both pain and itch input. Our results suggest that ORX neurons inversely regulate pain- and itch-related behaviors, which could be understood as a defense response to cope with stress environment.
BMAL1 plays a critical role in the protection against cardiac hypertrophy through autophagy in vitro
Authors: Yu Lei , Ren Lei , Dong Linchang
Published: August 2022

Background

Heart disease could result from a malfunction in the core clock gene BMAL1, according to studies conducted on animals and humans in vitro and in vivo. However, in pathological conditions, the role of BMAL1 was not clear. In the present study, we identified a potential link between BMAL1 and cardiac hypertrophy.

Methods

Primary cultured neonatal rat cardiomyocytes were stimulated by Ang II. Cardiomyocytes immunofluorescence analysis was performed to observe the cell size. RT-PCR and Western blot were used to find out the gene and protein expression. Cell apoptosis was measured by TUNEL staining. The Elisa assay was performed which determine the release of cytokines led to the activation of cardiac fibro-blasts in cell-free supernatants. Furthermore, gain- and loss-of-function studies revealed that BMAL1 has an effect on Ang II-induced cardiac hypertrophy.

Results

We found that Ang II-induced cardiac hypertrophy as a result BMAL1 expression was reduced. However, overexpression of BMAL1 could prevent Ang II-induced hypertrophy. Additionally, although BMAL1 overexpression in hypertrophic cardiomyocytes could not prevent hypertrophy, it did reduce the apoptosis of hypertrophic cardiomyocytes after Ang II had induced it. In addition, BMAL1 knockdown did not aggravate Ang II-induced hypertrophy but accelerated its development. Finally, BMAL1 overexpression significantly resisted the effects of Ang II on oxidative stress, autophagy and, cardiac fibrosis in cardiomyocytes.

Conclusions

Our results showed that overexpression of BMAL1 effectively resisted cardiac hypertrophy induced by Ang II. Our findings provided a novel potential target for the treatment of cardiac hypertrophy.
Undergraduate nursing students’ knowledge of and attitudes toward people with alzheimer’s disease
Authors: Aljezawi Ma’en , Al Qadire Mohammad , Suliman Mohammad , Al Omari Omar , Khalaf Atika
Published: August 2022

As the population ages, the number of people living with Alzheimer's disease is expected to grow; consequently, nursing students are expected to care for more people with Alzheimer's disease in their future careers. Exploring nursing students' level of knowledge and attitudes is essential here to fill any knowledge gap and enhance attitudes. For this reason, the current study aimed to measure the knowledge of and attitudes toward people living with Alzheimer's disease among undergraduate Jordanian nursing students. A descriptive cross-sectional design was utilized. Data were collected through an online questionnaire consisting of the Alzheimer's Disease Knowledge Scale (ADKS) and Dementia Attitudes Scale (DAS). A third part contained questions about previous formal education about Alzheimer's disease, reading Alzheimer's research, and the need for formal education about Alzheimer's disease. The study targeted all undergraduate Jordanian nursing students. A total of 275 students agreed to participate and completed the questionnaire. Jordanian nursing students had low knowledge regarding people living with Alzheimer's disease, with a mean ADKS score of 18.3 out of 30; however, their attitudes were positive, with a mean DAS score of 91 out of 140. There was no statistical difference in attitude or knowledge between different academic levels. The majority of students (90.5%) expressed their desire to have a formal education regarding Alzheimer's disease. Knowledge regarding people with Alzheimer's disease could be improved through training and education. Positive attitudes reported by students could augment the learning process.
Indicator-activities to apply primary health care principles in national or large-scale community health worker programs in low-and middle-income countries: a Delphi exercise
Authors: Perveen Shagufta , Laurence Caroline , Mahmood Mohammad Afzal
Published: August 2022

Introduction

Primary Health Care (PHC) gained considerable momentum in the past four decades and led to improved health outcomes across a wide variety of settings. In low-and middle-income countries (LMICs), national or large-scale Community Health Worker Programs (CHWPs) are considered as vehicles to incorporate PHC principles into healthcare provision and are an essential aspect of the PHC approach to achieve health for all and sustainable development goals. The success of CHWPs is rooted in the application of PHC principles. However, there is evidence that shows patchy implementation of PHC principles across national CHWPs in LMICs. This may reflect the lack of information on what activities would illustrate the application of these principles in CHWPs. This study aimed to identify a set of core/indicator-activities that reflect the application of PHC principles by CHWPs in LMICs.

Methods

A two-round modified Delphi study was undertaken with participants who have extensive experience in planning, implementation and evaluation of CHWPs. Survey design and analysis was guided by the four PHC principles namely Universal Health Coverage, Community Participation, Intersectoral Coordination and Appropriateness. Responses were collected using a secure online survey program (survey monkey). In round one, participants were asked to list ‘core activities’ that would reflect the application of each PHC principle and its sub-attributes and challenges to apply these principles in CHWPs. In round two, participants were asked to select whether they agree or disagree with each of the activities and challenges. Consensus was set a priori at 70% agreement of participants for each question.

Results

Seventeen participants from 15 countries participated in the study. Consensus was reached on 59 activities reflecting the application of PHC principles by CHWPs. Based on participants’ responses, a set of 29 indicator-activities for the four PHC principles was developed with examples for each indicator-activity.

Conclusion

These indicator-activities may provide guidance on how PHC principles can be implemented in CHWPs. They can be used in the development and evaluation of CHWPs, particularly in their application of PHC principles. Future research may focus on testing the utility of indicator-activities on CHWPs in LMICs.
Associations with oral health indices for obesity risk among Japanese men and women: results from the baseline data of a cohort study
Authors: Tanaka Hiroko , Nakano Mirei , Kuriki Kiyonori ,   Shizuoka-Sakuragaoka J-MICC Study Group
Published: August 2022

Background

Oral health is composed of various oral health indices (OHIs), such as oral self-care habits, oral hygiene, oral function, and mastication ability. Oral self-care habits have frequently been examined for obesity risk. This study aimed to comprehensively clarify the association between OHIs and obesity risk.

Methods

We collected data for 15 questions on the four OHIs and measured the body mass index of 3494 men and 2552 women aged 35–79 years. Obesity was defined as a body mass index ≥25 kg/m2. The four OHIs were scored by the corresponding questions (good as “reference”), and the summed score was defined as “comprehensive OHI”, that is, the fifth OHI. Each lowest tertile score was used as “reference”. Using multiple logistic regression analysis, odds ratios (ORs), 95% confidence intervals (CIs), and p-values for trends were estimated.

Results

In the men and women, the ORs were 1.37 (1.11–1.67, < 0.01) and 2.48 (1.80–3.42, < 0.01) for oral self-care habits, and 1.78 (1.42–2.24, < 0.01) and 3.06 (2.12–4.43, < 0.01) for tooth brushing frequency, respectively. Moreover, in men, a significant trend was found for “harder rinsing out your mouth”, related to “oral function”. In women, the ORs were 1.74 (1.28–2.36, < 0.01) and 1.43 (1.00–2.06, < 0.01) for “comprehensive OHI” and “longer meal time” related to “mastication ability”, respectively.

Conclusions

Our findings showed that obesity risk was associated with poor of oral health, which were comprehensively composed of various OHIs, among middle-aged and older Japanese men and women.
Undernotification and underreporting of tuberculosis in Zambia: a national data quality assessment
Authors: Lungu P. S. , Kabaso M. E. , Mihova R. , Silumesii A. , Chisenga T. , Kasapo C. , Mwaba I. , Kerkhoff A. D. , Muyoyeta M. , Chimzizi R. , Malama K.
Published: August 2022

Background

Despite national implementation of several high impact interventions and innovations to bolster tuberculosis (TB) detection and improve quality of TB services in Zambia, notifications have been declining since 2004. A countrywide data quality assessment (DQA) of Zambia’s National TB and Leprosy Programme (NTLP) was undertaken to quantify the degree to which undernotification and underreporting of TB notifications may be occurring.

Methods

The NTLP conducted a retrospective DQA of health facilities in high burden districts in all ten Zambian provinces. Multiple routine programmatic data sources were triangulated through a multi-step verification process to enumerate the total number of unique TB patients diagnosed between 1st January and 31st August 2019; both bacteriologically confirmed and clinically diagnosed TB patients were included. Undernotification was defined as the number of TB patients identified through the DQA that were not documented in facility treatment registers, while underreporting was defined as the number of notified TB cases not reported to the NTLP.

Results

Overall, 265 health facilities across 55 districts were assessed from which 28,402 TB patients were identified; 94.5% of TB patients were ≥ 15 years old, 65.1% were male, 52.0% were HIV-positive, and 89.6% were a new/relapse case. Among all TB cases, 32.8% (95%CI: 32.2–33.3) were unnotified. Undernotification was associated with age ≥ 15 years old (adjusted prevalence odds ratio [aPOR] = 2.4 [95%CI: 2.0–2.9]), HIV-positive status (aPOR = 1.6 [95%CI: 1.5–1.8]), being a new/relapse TB case (aPOR = 17.5 [95%CI: 13.4–22.8]), being a clinically diagnosed TB case (aPOR = 4.2 [95%CI:3.8–4.6]), and being diagnosed at a hospital (range, aPOR = 1.5 [95%CI: 1.3–1.6] to 2.6 [95%CI: 2.3–2.9]). There was substantial heterogeneity in the proportion of unnotified TB cases by province (range, 18.2% to 43.6%). In a sub-analysis among 22,199 TB patients with further data available, 55.9% (95%CI: 55.2–56.6) were notified and reported to the NTLP, 32.8% (95%CI: 32.2–33.4) were unnotified, and 11.3% (95%CI: 10.9–11.7) went unreported to the NTLP.

Conclusions

The findings from Zambia’s first countrywide TB programme DQA demonstrate substantial undernotification and underreporting of TB cases across all provinces. This underscores the urgent need to implement a robust and integrated data management system to facilitate timely registration and reporting of all TB patients who are diagnosed and treated.
Explorative study on scale cortisol accumulation in wild caught common dab (Limanda limanda)
Authors: Vercauteren Maaike , Ampe Bart , Devriese Lisa , Moons Christel Palmyre Henri , Decostere Annemie , Aerts Johan , Chiers Koen
Published: August 2022

Background

Flatfish live in a diverse marine ecosystem that is changing due to natural variations and anthropogenic influences. These changes can evoke a stress response mainly resulting in production of the glucocorticoid cortisol, which mediates effects on various levels of biological organization. The finding that cortisol accumulates in fish scales, offering a retrospective view on cortisol production, provides opportunities to use this matrix for chronic stress assessment. The present study is the first to gather information on scale cortisol concentration in wild-caught common dab (Limanda limanda), based on a two-pronged approach using (1) field measurements and (2) a laboratory in vivo-study where wild-caught dab were fed by cortisol-spiked feed during 30 or 90 days to demonstrate the possible accumulation of cortisol in the scales and to evaluate its impact on fish health.

Results

Based on the field measurements, the average scale cortisol concentration in wild-caught fish was 0.0034 ± 0.0046 µg kg−1 scale (n = 67). This indicates that wild common dab is indeed able to incorporate cortisol in the scales.

Based on the experimental data, the cortisol-fed fish showed an increased plasma cortisol concentration (80.16 ± 82.58 µg L−1) compared to the control group (4.54 ± 9.57 µg L−1) after 30 days of cortisol feeding. The increase in plasma cortisol concentration was positively correlated with an increased cortisol concentration in the scale after 30 days of cortisol-spiked feeding. This correlation was, however, no longer observed after 90 days of cortisol-spiked feeding. Interestingly, cortisol concentration of the scales on the pigmented side was significantly higher compared to the non-pigmented side. Some health parameters such as epidermal thickness, body condition and Ichthyobodo sp. parasitic infection showed a correlation with scale cortisol concentration after 30 days.

Conclusions

We have demonstrated that common dab is able to accumulate cortisol in its scales. This seems to occur proportionally to circulating concentrations of plasma cortisol in fish fed with cortisol supplemented feed after 30 days.
Predictive potential of ACE phenotyping in extrapulmonary sarcoidosis
Authors: Danilov Sergei M. , Kurilova Olga V. , Sinitsyn Valentin E. , Kamalov Armais A. , Garcia Joe G. N. , Dudek Steven M.
Published: August 2022

Elevated ACE expression in tissues (reflected by blood ACE levels) is associated with increased risk of cardiovascular diseases and is also a marker for granulomatous diseases. We developed a new approach for characterization of ACE status in the blood—ACE phenotyping and established normal values of ACE levels 50–150% of control pooled plasma. ACE phenotyping was performed in citrated plasma of 120 patients with known interstitial lung diseases. In the 1st set of 100 patients we found 22 patients with ACE levels > 150%; ACE phenotyping also objectively identified the presence of ACE inhibitors in the plasma of 15 patients. After excluding these patients and patient with ACE mutation that increases ACE shedding, 17 patients were identified as a suspicious for systemic sarcoidosis based on elevation of blood ACE (> 150% of mean). A new parameter that we have established–ACE immunoreactivity (with mAb 9B9)—allowed us to detect 22 patients with decreased values (< 80%) of this parameter, which may indicate the presence of ACE in the blood that originates from macrophages/dendritic cells of granulomas. In the remaining 20 patients, this new parameter (mAbs binding/activity ratio) was calculated using 3 mAbs (9B9, 3A5 and i1A8—having overlapping epitopes), and 8 patients were identified as having decreases in this parameter, thus increasing dramatically the sensitivity for detection of patients with systemic sarcoidosis. Whole body PET scan confirmed extrapulmonary granulomas in some patients with lower immunoreactivity towards anti-ACE mAbs. ACE phenotyping has novel potential to noninvasively detect patients with systemic sarcoidosis.
Critical policies disparity of the first and second waves of COVID-19 in the United Kingdom
Authors: Yang Manfei , Shi Leiyu , Chen Haiqian , Wang Xiaohan , Jiao Jun , Liu Meiheng , Yang Junyan , Sun Gang
Published: August 2022

Objective

This study aims to compare the differences in COVID-19 prevention and control policies adopted by the United Kingdom (UK) during the first wave (31 January 2020 to 6 September 2020) and the second wave (7 September 2020 to 12 April 2021), and analyze the effectiveness of the policies, so as to provide empirical experience for the prevention and control of COVID-19.

Methods We systematically summarized the pandemic prevention and control policies of the UK from official websites and government documents, collated the epidemiological data from 31 January 2020 to 12 April 2021, and analyzed the effectiveness of the two waves of pandemic prevention and control policies.

Results

The main pandemic prevention and control policies adopted by the UK include surveillance and testing measures, border control measures, community and social measures, blockade measures, health care measures, COVID-19 vaccination measure, and relaxed pandemic prevention measures. The new cases per day curve showed only one peak in the first wave and two peaks in the second wave. The number of new cases per million in the second wave was much higher than that in the first wave, and the curve fluctuated less. The difference between mortality per million was small, and the curve fluctuated widely.

Conclusion

During the first and second waves of COVID-19, the UK implemented three lockdowns and managed to slow the spread of the pandemic. The UK’s experience in mitigating the second wave proves that advancing COVID-19 vaccination needs to be accompanied by ongoing implementation of non-pharmacological interventions to reduce the transmission rate of infection. And a stricter lockdown ensures that the containment effect is maximized during the lockdown period. In addition, these three lockdowns featured distinct mitigation strategies and the UK’s response to COVID-19 is mitigation strategy that reduce new cases in the short term, but with the risk of the pandemic rebound.
Very severe immune thrombocytopenia following SARS-CoV-2 vaccination requiring splenectomy: a case report
Authors: Weiner Marc , Rodriguez-Vigouroux Robert , Masouridi-Levrat Stavroula , Samii Kaveh
Published: August 2022

Background

Some conventional vaccines have been recognized as a cause of secondary immune thrombocytopenia (ITP). According to recent publications, mRNA vaccines are probably associated with an increased risk of ITP.

Case presentation

Our patient developed severe ITP one week after the second dose of COVID-19 mRNA vaccine. Medical management was not effective, requiring splenectomy to obtain sustained remission.

Conclusion

Considering the temporality and immunological hypothesis, we consider the vaccine to be the trigger of this ITP. To our knowledge, our case is, to date, the most severe case of ITP reported following SARS-CoV-2 vaccination and could help for the therapeutic management of similar patients.
Shorter telomere length is associated with COVID-19 hospitalization and with persistence of radiographic lung abnormalities
Authors: Retuerto Miriam , Lledó Ana , Fernandez-Varas Beatriz , Guerrero-López Rosa , Usategui Alicia , Lalueza Antonio , García-García Rocío , Mancebo Esther , Paz-Artal Estela , Sastre Leandro , Perona Rosario , Pablos José L.
Published: August 2022

Background

Age and comorbidity are the main determinants of COVID-19 outcome. Shorter leukocyte telomere length (TL), a hallmark of biological aging, has been associated with worse COVID-19 outcomes. We sought to determine TL in patients with severe COVID-19 requiring hospitalization to analyze whether clinical outcomes and post-COVID-19 manifestations are associated with shorter TL.

Results

We analyzed 251 patients with PCR-confirmed COVID-19, hospitalized in the first months of the pandemics. We determined TL in PBL at admission by quantitative-PCR (qPCR) analysis in patients. A healthy cohort from the same area with a similar age range (n = 169) was used to calculate TL Z-scores. After hospital discharge, 144 COVID-19 survivors were followed-up for persistent COVID-19 manifestations. A second TL determination was performed in a smaller group of 63 patients 1 year later and compared with baseline TL.

Hospitalized COVID-19 patients had a decreased baseline age-adjusted TL Z-score compared to the reference group. No differences in Z-scores were observed in patients with different COVID-19 outcomes, classified as WHO ordinal scores. In 144 patients, followed for a median of 8 months, post-COVID manifestations were not associated to differences in TL. Persistence of lung radiographic abnormalities was associated with shorter baseline TL. In patients with a second TL determination, further telomere shortening (TS) was observed in 35% and telomere lengthening in 49%. Patients with further TS had suffered a more severe disease.

Conclusion

Shorter TL is associated with COVID-19 hospitalization but not with hospital clinical outcomes nor with persistent post-COVID-19 manifestations. Delayed resolution of radiographic lung abnormalities was also associated with shorter TL.
Clinical adoption patterns of 0.35 Tesla MR-guided radiation therapy in Europe and Asia
Authors: Slotman Berend J. , Clark Mary Ann , Özyar Enis , Kim Myungsoo , Itami Jun , Tallet Agnès , Debus Jürgen , Pfeffer Raphael , Gentile PierCarlo , Hama Yukihiro , Andratschke Nicolaus , Riou Olivier , Camilleri Philip , Belka Claus , Quivrin Magali , Kim BoKyong , Pedersen Anders , van Overeem Felter Mette , Kim Young Il , Kim Jin Ho , Fuss Martin , Valentini Vincenzo
Published: August 2022

Background

Magnetic resonance-guided radiotherapy (MRgRT) utilization is rapidly expanding, driven by advanced capabilities including better soft tissue imaging, continuous intrafraction target visualization, automatic triggered beam delivery, and the availability of on-table adaptive replanning. Our objective was to describe patterns of 0.35 Tesla (T)-MRgRT utilization in Europe and Asia among early adopters of this novel technology.

Methods

Anonymized administrative data from all 0.35T-MRgRT treatment systems in Europe and Asia were extracted for patients who completed treatment from 2015 to 2020. Detailed treatment information was analyzed for all MR-linear accelerators (linac) and -cobalt systems.

Results

From 2015 through the end of 2020, there were 5796 completed treatment courses delivered in 46,389 individual fractions. 23.5% of fractions were adapted. Ultra-hypofractionated (UHfx) dose schedules (1–5 fractions) were delivered for 63.5% of courses, with 57.8% of UHfx fractions adapted on-table. The most commonly treated tumor types were prostate (23.5%), liver (14.5%), lung (12.3%), pancreas (11.2%), and breast (8.0%), with increasing compound annual growth rates (CAGRs) in numbers of courses from 2015 through 2020 (pancreas: 157.1%; prostate: 120.9%; lung: 136.0%; liver: 134.2%).

Conclusions

This is the first comprehensive study reporting patterns of utilization among early adopters of a 0.35T-MRgRT system in Europe and Asia. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of on-table adaptive RT have accelerated a transition to UHfx regimens. MRgRT has been predominantly used to treat tumors in the upper abdomen, pelvis and lungs, and increasingly with adaptive replanning, which is a radical departure from legacy radiotherapy practices.
Sutureless aortic valve replacement in pure aortic regurgitation: expanding the indications
Authors: Zubarevich Alina , Rad Arian Arjomandi , Amanov Lukman , Szczechowicz Marcin , Osswald Anja , Torabi Saeed , Schmack Bastian , Ruhparwar Arjang , Weymann Alexander
Published: August 2022

Background

In the era of transcatheter methods, patients presenting with a pure aortic regurgitation (AR) are not considered eligible for transcatheter treatment and therefore require another less invasive surgical option. We sought to review our experience with sutureless aortic valve replacement (SU-AVR) in patients presenting with symptomatic pure AR, which until now is a contraindication for implementation of sutureless valve prostheses in Europe.

Methods

Between April 2018 and June 2021, 80 consecutive patients underwent a SU-AVR for various indications at our institution. We analyzed the outcomes and postoperative complications of 12 patients presenting with a pure severe AR undergoing SU-AVR using Perceval (Corcym).

Results

The mean age of the patients was 67 ± 9.1 years old. All patients presented with symptomatic pure AR. Patients presented with multiple comorbidities as reflected by the mean EuroSCORE-II of 3.6 ± 2.6%. Six patients (50%) underwent a concomitant CABG procedure. The mean operating- and cross clamp time was 127.25 ± 45.9 and 40.33 ± 17.3 min respectively. All isolated SU-AVR were performed via J-sternotomy or right anterolateral thoracotomy. There were no cases of device dislocation. No patients presented with a paravalvular leakage. We observed excellent mean postoperative pressure gradient at follow-up 5.7 ± 1.5 mmHg.

Conclusions

Our experience with SU-AVR shows the feasibility of sutureless technologies in the aortic valve surgery due to pure AR. Besides the great technical success and excellent hemodynamics, SU-AVR in severe AR offers a great opportunity of reducing the invasivity of the surgical procedure and potentially reducing hospital cost without compromising the postoperative outcomes and in-hospital length of stay.
Fisetin induces DNA double-strand break and interferes with the repair of radiation-induced damage to radiosensitize triple negative breast cancer cells
Authors: Khozooei Shayan , Lettau Konstanze , Barletta Francesca , Jost Tina , Rebholz Simone , Veerappan Soundaram , Franz-Wachtel Mirita , Macek Boris , Iliakis George , Distel Luitpold V. , Zips Daniel , Toulany Mahmoud
Published: August 2022

Background

Triple-negative breast cancer (TNBC) is associated with aggressiveness and a poor prognosis. Besides surgery, radiotherapy serves as the major treatment modality for TNBC. However, response to radiotherapy is limited in many patients, most likely because of DNA damage response (DDR) signaling mediated radioresistance. Y-box binding protein-1 (YB-1) is a multifunctional protein that regulates the cancer hallmarks among them resisting to radiotherapy-induced cell death. Fisetin, is a plant flavonol of the flavonoid family of plant polyphenols that has anticancer properties, partially through inhibition of p90 ribosomal S6 kinase (RSK)-mediated YB-1 phosphorylation. The combination of fisetin with radiotherapy has not yet been investigated.

Methods

Activation status of the RSK signaling pathway in total cell lysate and in the subcellular fractions was analyzed by Western blotting. Standard clonogenic assay was applied to test post-irradiation cell survival. γH2AX foci assay and 3 color fluorescence in situ hybridization analyses were performed to study frequency of double-strand breaks (DSB) and chromosomal aberrations, respectively. The underlying repair pathways targeted by fisetin were studied in cells expressing genomically integrated reporter constructs for the DSB repair pathways via quantifying the expression of green fluorescence protein by flow cytometry. Flow cytometric quantification of sub-G1 cells and the protein expression of LC3-II were employed to measure apoptosis and autophagy, respectively. Kinase array and phosphoproteomics were performed to study the effect of fisetin on DDR response signaling.

Results

We showed that the effect of fisetin on YB-1 phosphorylation in TNBC cells is comparable to the effect of the RSK pharmacological inhibitors. Similar to ionizing radiation (IR), fisetin induces DSB. Additionally, fisetin impairs repair of IR-induced DSB through suppressing the classical non-homologous end-joining and homologous recombination repair pathways, leading to chromosomal aberration as tested by metaphase analysis. Effect of fisetin on DSB repair was partially dependent on YB-1 expression. Phosphoproteomic analysis revealed that fisetin inhibits DDR signaling, which leads to radiosensitization in TNBC cells, as shown in combination with single dose or fractionated doses irradiation.

Conclusion

Fisetin acts as a DSB-inducing agent and simultaneously inhibits repair of IR-induced DSB. Thus, fisetin may serve as an effective therapeutic strategy to improve TNBC radiotherapy outcome.
The efficacy and safety of angiogenesis inhibitors for recurrent ovarian cancer: a meta‑analysis
Authors: Zhang Chunmei , Zhao Wancheng
Published: August 2022

Objective

To investigate the efficacy and safety of angiogenesis inhibitors in the treatment of recurrent ovarian cancer (OC).

Methods

Electronic databases including PubMed, Web of Science, and the Cochrane Library were searched to find eligible studies until August 10, 2021. The data on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were pooled. Furthermore, grade ≥ 3 adverse events (AEs) were investigated.

Results

A total of 13 studies with 3953 patients were included. Compared with control group, angiogenesis inhibitors resulted in significant improvement in PFS (hazard ratio (HR) = 0.61, 95%CI, 0.54–0.69), OS (HR = 0.88, 95%CI, 0.81–0.95), and ORR (odds ratio (OR) = 2.15, 95% CI, 1.74–2.65). However, angiogenesis inhibitors were associated with a higher risk of grade ≥ 3 AEs (relative risk (RR), 1.20, 95% CI, 1.04–1.38).

Conclusion

Angiogenesis inhibitors can improve ORR, PFS, and OS in patients with recurrent OC, but they can increase the incidence of AEs ≥ 3.
Human dyskerin binds to cytoplasmic H/ACA-box-containing transcripts affecting nuclear hormone receptor dependence
Authors: Zacchini Federico , Venturi Giulia , De Sanctis Veronica , Bertorelli Roberto , Ceccarelli Claudio , Santini Donatella , Taffurelli Mario , Penzo Marianna , Treré Davide , Inga Alberto , Dassi Erik , Montanaro Lorenzo
Published: August 2022

Background

Dyskerin is a nuclear protein involved in H/ACA box snoRNA-guided uridine modification of RNA. In humans, its defective function is associated with cancer development and induces specific post-transcriptional alterations of gene expression. In this study, we seek to unbiasedly identify mRNAs regulated by dyskerin in human breast cancer-derived cells.

Results

We find that dyskerin depletion affects the expression and the association with polysomes of selected mRNA isoforms characterized by the retention of H/ACA box snoRNA-containing introns. These snoRNA retaining transcripts (snoRTs) are bound by dyskerin in the cytoplasm in the form of shorter 3′ snoRT fragments. We then characterize the whole cytoplasmic dyskerin RNA interactome and find both H/ACA box snoRTs and protein-coding transcripts which may be targeted by the snoRTs’ guide properties. Since a fraction of these protein-coding transcripts is involved in the nuclear hormone receptor binding, we test to see if this specific activity is affected by dyskerin. Obtained results indicate that dyskerin dysregulation may alter the dependence on nuclear hormone receptor ligands in breast cancer cells. These results are paralleled by consistent observations on the outcome of primary breast cancer patients stratified according to their tumor hormonal status. Accordingly, experiments in nude mice show that the reduction of dyskerin levels in estrogen-dependent cells favors xenograft development in the absence of estrogen supplementation.

Conclusions

Our work suggests a cytoplasmic function for dyskerin which could affect mRNA post-transcriptional networks relevant for nuclear hormone receptor functions.
Sorbicillinoids hyperproduction without affecting the cellulosic enzyme production in Trichoderma reesei JNTR5
Authors: Li Chengcheng , Gu Ruihan , Lin Fengming , Xiao Huining
Published: August 2022

Background

Microbial production of bioactive secondary metabolites is challenging as most of the encoding genes are silent; and even if they are activated, the biosynthetic pathways are usually complex. Sorbicillinoids with multifunctional bioactivities are examples of these problems, which if solved can result in a more sustainable, simple supply of these important compounds to the pharmaceutical industry. As an excellent producer of cellulosic enzymes, Trichoderma reesei can secrete various sorbicillinoids.

Results

Here, we obtained a T. reesei mutant strain JNTR5 from the random mutation during overexpression of gene Tr69957 in T. reesei RUT-C30. JNTR5 exhibited a significant constitutive increase in sorbicillinoids production without affecting the cellulosic enzyme production. Confocal laser scanning microscope (CLSM) results indicated that sorbicillinoids were distributed in both mycelium and spores of JNTR5 with blue and green fluorescence. Compared with RUT-C30, JNTR5 displayed different cell morphology, reduced growth rate, and increased sporulation, but a similar biomass accumulation. Furthermore, transcriptome analysis revealed that all genes belonging to the sorbicillinoid gene cluster were upregulated, while most cellulase-encoding genes were downregulated. The cell wall integrity of JNTR5 was damaged, which might benefit the cellulase secretion and contribute to the almost unchanged cellulase and hemicellulase activity given that the damaged cell wall can enhance the secretion of the enzymes.

Conclusions

For the first time, we constructed a sorbicillinoids hyperproduction T. reesei platform with comparable cellulosic enzymes production. This outperformance of JNTR5, which is strain-specific, is proposed to be attributed to the overexpression of gene Tr69957, causing the chromosome remodeling and subsequently changing the cell morphology, structure, and the global gene expression as shown by phenotype and the transcriptome analysis of JNTR5. Overall, JNTR5 shows great potential for industrial microbial production of sorbicillinoids from cellulose and serves as an excellent model for investigating the distribution and secretion of yellow pigments in T. reesei.