bluuebunny/crossref_metadata_2025 huggingface dataset:
Disturbances of the Gut Microbiota, Sleep Architecture, and mTOR Signaling Pathway in Patients with Severe Obstructive Sleep Apnea-Associated Hypertension
Authors: Ko Chih-Yuan , Su Huan-Zhang , Zhang Li , Zeng Yi-Ming
Published: November 2021

Intermittent hypoxia and sleep fragmentation are pathophysiological processes involved in obstructive sleep apnea (OSA) which affect gut microbiota, sleep architecture, and mTOR signaling pathway. However, the involvement of these elements in the pathogenesis mechanism of OSA-associated hypertension remains unclear. Therefore, this study investigated whether the OSA-associated hypertension mechanism is regulated by the gut microbiota and mTOR signaling pathway. Patients were diagnosed by polysomnography; their fecal samples were obtained and analyzed for their microbiome composition by 16S ribosomal RNA pyrosequencing and bioinformatics analysis. Transcript genes on fasting peripheral blood mononuclear cells (PBMCs) were examined using Illumina RNA-sequencing analysis. Totally, we enrolled 60 patients with severe OSA [without hypertension (n = 27) and with hypertension (n = 33)] and 12 controls (neither OSA nor hypertension). Results revealed that severe-OSA patients with hypertension had an altered gut microbiome, decreased short-chain fatty acid-producing bacteria

P
<
0.05

, and reduced arginine and proline metabolism pathways

P
=
0.001

, compared with controls; also, they had increased stage N1 sleep and reduced stages N2 and N3 sleep accompanied by repeated arousals

P
<
0.05

. Analysis of PBMCs using the Kyoto Encyclopedia of Genes and Genomes database showed that the mTOR signaling pathway

P

=

0.006

was the most important differential gene-enriched pathway in severe-OSA patients with hypertension. Our findings extend prior work and suggest a possibility that the regulation of the mTOR signaling pathway is involved in developing OSA-associated hypertension through its interaction with the disturbance of the gut microbiome and sleep architecture.
BusCount: A Provable Replay Protection Solution for Automotive CAN Networks
Authors: Zelle Daniel , Gürgens Sigrid
Published: November 2021

Information technology has become eminent in the development of modern cars. More than 50 Electronic Control Units (ECUs) realize vehicular functions in hardware and software, ranging from engine control and infotainment to future autonomous driving systems. Not only do the connections to the outside world pose new threats, but also the in-vehicle communication between ECUs, realized by bus systems such as Controller Area Network (CAN), needs to be protected against manipulation and replay of messages. Multiple countermeasures were presented in the past making use of Message Authentication Codes and time stamps and message counters, respectively, to provide message freshness, most prominently AUTOSAR’s Secure Onboard Communication (SecOC). In this paper, we focus on the latter ones. As one aspect of this paper, using an adequate formal model and proof, we will show that the currently considered solutions exhibit deficiencies that are hard if not impossible to overcome within the scope of the respective approaches. We further present a hardware-based approach that avoids these deficiencies and formally prove its freshness properties. In addition, we show its practicability by a hardware implementation. Finally, we evaluate our approach in comparison to counter-based solutions currently being used.
Inevitable Progress—Relying on the Immune System, Not Chance
Authors: Sacco Assuntina G. , Cohen Ezra E.W.
Published: November 2021

Locoregional recurrence of head and neck cancer after curative therapy portends a poor prognosis even when resectable. Immunotherapy has opened the door to novel strategic approaches in the curative treatment paradigm. Potentially improving outcomes for patients with recurrent, resectable disease through combination immune modulators highlights a new frontier.

See related article by Hanna et al., p. 468
Relation between Oscillometric Measurement of Central Hemodynamics and Left Ventricular Hypertrophy in Hypertensive Patients
Authors: Obayashi Masakazu , Kobayashi Shigeki , Nanno Takuma , Hamada Yoriomi , Yano Masafumi
Published: November 2021

Introduction: The augmentation index (AIx) or central systolic blood pressure (SBP), measured by radial applanation tonometry, has been reported to be independently associated with left ventricular hypertrophy (LVH) in Japanese hypertensive patients. Cuff-based oscillometric measurement of the AIx using Mobil-O-Graph® showed a low or moderate agreement with the AIx measurement with other devices. Methods: The AIx measured using the Mobil-O-Graph was validated against the tonometric measurements of the radial AIx measured using HEM-9000AI in 110 normotensive healthy individuals (age, 21–76 years; 50 men). We investigated the relationship between the central hemodynamics assessed using the Mobil-O-Graph and LVH in 100 hypertensive patients (age, 54–75 years; 48 men), presenting a wall thickness of ≥11 mm and ≥10 mm in men and women, respectively. Results: Although the Mobil-O-Graph-measured central AIx showed no negative values, it correlated moderately with the HEM-9000AI-measured radial AIx (r = 0.602, p < 0.001) in the normotensive individuals. The hypertensive patients did not show a significant difference in the central SBP between the sexes, but the central AIx was lower in men than in women. The independent determinants influencing left ventricle (LV) mass index (LVMI) (R2 = 0.362; adjusted R2 = 0.329, p < 0.001) were heart rate (β = −0.568 ± 0.149, p < 0.001), central SBP (β = 0.290 ± 0.100, p = 0.005), and aortic root diameter (β = 1.355 ± 0.344, p = 0.001). Age (β = −0.025 ± 0.124, p = 0.841) and the central AIx (β = 0.120 ± 0.131, p = 0.361) were not independently associated with the LVMI. The area under the receiver operator characteristic curve to evaluate the diagnostic performance of the central AIx for the presence of LVH (LVMI >118 g/m2 in men or >108 g/m2 in women) was statistically significant in men (0.875, p < 0.001) but not in women (0.622, p = 0.132). In men, a central AIx of 28.06% had a sensitivity of 83.3% and specificity of 80.0% for detecting LVH. Conclusions: AIx measurement in men provided useful prognostic information for the presence of LVH. Pulse-wave analysis assessed using the Mobil-O-Graph may be a valuable tool for detecting LVH in hypertensive patients.
Recurrence of Pemphigus Vulgaris after Bilateral Breast Irradiation: A Case Report and Review of the Literature
Authors: Invernizzi Camille , Gaultier Victor , Guilbert Philippe , Jouannaud Christelle , Labrousse Anne-Laure , Marchand Crety Charles
Published: November 2021

Pemphigus is a serious and rare chronic bullous autoimmune disease. It is characterized by mucocutaneous erosions secondary to autoantibodies directed against desmogleins 1 and 3, proteins involved in intercellular adhesion mechanisms. The occurrence of pemphigus is based on the triggering of genetic and external environmental factors such as drugs, infection, and more rarely radiotherapy. To date, only 16 cases of radiation-induced pemphigus are described in the context of breast cancer treatment. We present the case of a 76-year-old woman who had a recurrence of pemphigus vulgaris limited to the irradiation field after exposure to an adjuvant radiotherapy treatment for a bilateral triple-negative breast cancer. The onset was bilateral limited to the irradiation area and was treated effectively with local and systemic corticosteroids. After a rigorous review of the literature, only 16 cases of breast cancer radiation-induced pemphigus appeared. In contrast to several cases, the rash was limited to the irradiated area and improved with systemic corticosteroids. For more than three-quarters of the described cases in the literature, pemphigus occurs within 3 months following the end of treatment. After systemic immunosuppressive treatment, this disease disappears in the vast majority of the reported cases.
Development of a Model to Predict Liver Decompensation prior to Transarterial Chemoembolization Refractoriness in Patients with Intermediate-Stage Hepatocellular Carcinoma
Authors: Ferreira-Silva Joel , Costa-Moreira Pedro , Cardoso Helder , Liberal Rodrigo , Pereira Pedro , Macedo Guilherme
Published: November 2021

Introduction: Transarterial chemoembolization (TACE) is the first-line treatment for patients with intermediate-stage hepatocellular carcinoma (HCC). For patients without an adequate response, current finding suggests that treatment with molecular target agents, approved for advanced stage, might present benefits. However, this requires a preserved liver function. This study aims to evaluate possible predictors of early deterioration of hepatic reserve, prior to TACE refractoriness, in a cohort of patients treated with TACE. Methods: Retrospective analysis of 99 patients withChild-Pugh class A and intermediate-stage HCC who underwent TACE as the first-line treatment. All patients were submitted to a biochemical and medical evaluation prior to initial TACE and every month afterward. Response to initial TACE was evaluated at 1 month. The time to Child-Pugh class deterioration before TACE refractoriness was assessed. Results: Ninety-nine patients were included. Objective response rate (ORR) to initial TACE was assessed as present in 59 (63.4%) and as absent in 34 (36.6%) patients. Liver decompensated before TACE refractoriness in 51 (51.5%) patients, and the median time to liver decompensation was 14 (IQR 8–20) months after first TACE. In multivariate analysis, beyond up-to-7 criteria (HR 2.4, p = 0.031), albumin <35 mg/dL (HR 3.5, p < 0.001) and absence of ORR (HR 2.4, p = 0.020) were associated with decreased overall survival free of liver decompensation. Moreover, beyond up-to-7 criteria, albumin <35 mg/dL and absence of ORR associated negatively with 6-month survival free of liver decompensation. Our model created using those variables was able to predict liver decompensation at 6 months with an AUROC of 0.701 (p = 0.02). Conclusions: The absence of ORR after initial TACE, beyond up-to-7 criteria and albumin <35 mg/dL, was a predictive factor for early liver decompensation before TACE refractoriness in our population. Such patients might benefit from treatment escalation to systemic therapy, in monotherapy or in combination with TACE.
COVID-19: Wann muss ich an MIS-A denken?
Authors: Keymel Stefanie
Published: November 2021

Multisystem inflammatory syndrome in adults (MIS-A) came to attention back in June 2020, when the United States Center for Disease Control and Prevention (CDC) received initial reports regarding patients who had presented delayed and multisystem involvement of the disease, with clinical course resembling multisystem inflammatory syndrome in children (MIS-C). This study introduces a case of MIS-A, where the patient presented 3 weeks after initial COVID-19 exposure. His clinical course was consistent with the working definition of MIS-A as specified by the CDC. Aggressive supportive care in the intensive care unit, utilization of advanced heart failure devices, and immunomodulatory therapeutics (high-dose steroids, anakinra, intravenous immunoglobulin) led to clinical recovery. Management of MIS-A is a topic of ongoing research and needs more studies to elaborate on treatment modalities and clinical predictors.
Invaluable Role of Consanguinity in Providing Insight into Paediatric Endocrine Conditions: Lessons Learnt from Congenital Hyperinsulinism, Monogenic Diabetes, and Short Stature
Authors: Amaratunga Shenali Anne , Tayeb Tara Hussein , Dusatkova Petra , Pruhova Stepanka , Lebl Jan
Published: November 2021

Consanguineous families have often played a role in the discovery of novel genes, especially in paediatric endocrinology. At this time, it has been estimated that over 8.5% of all children worldwide have consanguineous parents. Consanguinity is linked to demographic, cultural, and religious practises and is more common in some areas around the world than others. In children with endocrine conditions from consanguineous families, there is a greater probability that a single-gene condition with autosomal recessive inheritance is causative. From 1966 and the first description of Laron syndrome, through the discovery of the first KATP channel genes ABCC8 and KCNJ11 causing congenital hyperinsulinism (CHI) in the 1990s, to recent discoveries of mutations in YIPF5 as the first cause of monogenic diabetes due to the disruption of the endoplasmic reticulum (ER)-to-Golgi trafficking in the β-cell and increased ER stress; positive genetic findings in children from consanguinity have been important in elucidating novel genes and mechanisms of disease, thereby expanding knowledge into disease pathophysiology. The aim of this narrative review was to shed light on the lessons learned from consanguineous pedigrees with the help of 3 fundamental endocrine conditions that represent an evolving spectrum of pathophysiological complexity – from CHI, a typically single-cell condition, to monogenic diabetes which presents with uniform biochemical parameters (hyperglycaemia and glycosuria), despite varying aetiologies, up to the genetic regulation of human growth – the most complex developmental phenomenon.
Family History of Breast Cancer Is Associated with Elevated Risk of Prostate Cancer: Evidence for Shared Genetic Risks
Authors: Calvo Chozas Adrián , Mahjani Behrang , Rönnegård Lars
Published: November 2021

Introduction: Although breast and prostate cancers arise in different organs and are more frequent in the opposite sex, multiple studies have reported an association between their family history. Analysis of single nucleotide polymorphism data, based on distant relatives, has revealed a small positive genetic correlation between these cancers explained by common variants. The estimate of genetic correlation based on close relatives reveals the extent to which shared genetic risks are explained by both common and rare variants. This estimate is unknown for breast and prostate cancer. Method: We estimated the relative risks, heritability, and genetic correlation of breast cancer and prostate cancer based on the Minnesota Breast and Prostate Cancer Study, a family study of 141 families ascertained for breast cancer. Results: Heritability of breast cancer was 0.34 (95% credible interval: 0.23–0.49) and 0.65 (95% credible interval: 0.36–0.97) for prostate cancer, and the genetic correlation was 0.23. In terms of odds ratios, these values correspond to a 1.3 times higher odds of breast cancer among probands, given that the brother has prostate cancer. Conclusion: This study shows the inherent relation between prostate cancer and breast cancer; an incident of one in a family increases the risk of developing the other. The large difference between estimates of genetic correlation from distant and close relatives, if replicated, suggests that rare variants contribute to the shared genetic risk of breast and prostate cancer. However, the difference could stem from genotype-by-family effects shared between the two types of cancers.
Exercise-Induced Adrenocorticotropic Hormone Response Is Cooperatively Regulated by Hypothalamic Arginine Vasopressin and Corticotrophin-Releasing Hormone
Authors: Takahashi Kanako , Shima Takeru , Soya Mariko , Yook Jang Soo , Koizumi Hikaru , Jesmin Subrina , Saito Tsuyoshi , Okamoto Masahiro , Soya Hideaki
Published: November 2021

Introduction: Exercise becomes a stress when performed at an intensity above the lactate threshold (LT) because at that point the plasma adrenocorticotropic hormone (ACTH), a marker of stress response, increases. It is possible that the exercise-induced ACTH response is regulated at least by arginine vasopressin (AVP) and possibly by corticotropin-releasing hormone (CRH), but this remains unclear. To clarify the involvement of these factors, it is useful to intervene pharmacologically in the regulatory mechanisms, with a physiologically acceptable exercise model. Methods: We used a special stress model of treadmill running (aerobic exercise) for male Wistar rats, which mimic the human physiological response, where plasma ACTH levels increase at just above the LT for 30 min. Animals were administered the AVP V1b receptor antagonist SSR149415 (SSR) and/or the CRH type 1 receptor antagonist CP154526 (CP) intraperitoneally before the exercise, which allowed the monitoring of exercise-induced ACTH response. Immunohistochemical evaluation of activated AVP and CRH neurons with exercise was performed for the animals’ hypothalami. Results: A single injection of either antagonist, SSR or CP, resulted in inhibited ACTH levels after exercise stress. Moreover, the combined injection of SSR and CP strongly suppressed ACTH secretion during treadmill running to a greater extent than each alone. The running-exercise-induced activation of both AVP and CRH neurons in the hypothalamus was also confirmed. Conclusion: These results lead us to hypothesize that AVP and CRH are cooperatively involved in exercise-induced ACTH response just above the LT. This may also reflect the stress response with moderate-intensity exercise in humans.
КЛАСТЕРИЗАЦІЯ ФУНКЦІОНАЛЬНИХ СТАНІВ ОРГАНІЗМУ. ПІЛОТНЕ ДОСЛІДЖЕННЯ
Authors: Мінцер О. П. , Карленко В. П. , Шевченко Я. О. , Суханова О. О.
Published: November 2021

Розглянуто питання та проведено пілотний аналіз даних про можливості виділення стабільних станів функціонування організму при фізичних навантаженнях. В якості прикладу обрано показники ергоспірометрії та динаміки частоти серцевих скорочень у 7 чоловіків і 6 жінок, основного складу збірної команди України з біатлону. Визначено можливість виділення кластерів сталих фізіологічних станів спортсменів-біатлоністів, їх повторюваність, взаємозв'язок із фізіологічними показниками та виявлено бар'єри, що негативно впливають на своєчасне корегування функціонального стану спортсменів. З'ясовано, що проведена кластеризація функціонального стану в спортсменів у процесі змагальної діяльності підтвердила гіпотезу про наявність у них декількох сталих станів, виявлення та інтерпретація змін яких для досягнення максимального результату на змаганнях можлива при забезпеченні певної тривалості моніторингу та персоналізованого оцінювання траєкторії змін. Більшість методів автоматичної кластеризації станів у спортсменів дають близькі результати. Враховуючи, що біологічні об'єкти здатні створювати свої власні норми та постійно гармонізувати свої можливості для забезпечення стабільності функціонування, вкрай потрібна формалізація біологічних концепцій про сталі стани. Застосування парадигми сталих станів як комбінації незмінних фізіологічних показників (при не екстремальних впливах зовнішніх факторів) дозволяє суттєво полегшити вирішення завдання прогнозування результатів тренувального процесу в спортсменів.
ІНФОРМАЦІЙНИЙ АНАЛІЗ ДЕНТАЛЬНОЇ ІМПЛАНТАЦІЇ У ВІЙСЬКОВОСЛУЖБОВЦІВ ІЗ ВТОРИННОЮ АДЕНТІЄЮ ТА РЕКОМЕНДАЦІЇ ЩОДО ЇЇ ЛІКУВАННЯ
Authors: Лищишин М. З. , Пономаренко В. О. , Коваленко В. В. , Угрин М. М.
Published: November 2021

У статті на основі статистичного аналізу інформації про дентальну імплантацію у військовослужбовців із вторинною адентією проведено аналіз результатів лікування та на основі узагальнення результатів обґрунтовано рекомендації щодо вдосконалення лікування. Для дослідження розроблено класифікацію показів до дентальної імплантації у військовослужбовців Збройних Сил України, Що базується на їх розподілі за соціальними та клінічними параметрами. За соціальними параметрами визначено такі групи: військовослужбовці з наслідками бойових ушкоджень щелепно-лицевої ділянки; військовослужбовці, які отримали бойові поранення інших анатомічних ділянок; інші військовослужбовці. За клінічними параметрами — військовослужбовці з вторинною адентією, заміщення дефектів у яких незнімними ортопедичними конструкціями можливе лише при використанні дентальної імплантації; військовослужбовці з вторинною адентією, заміщення дефектів у яких незнімними конструкціями можливе як класичними мостоподібними протезами, так і при використанні дентальної імплантації (метод вибору); військовослужбовці з вторинною адентією, проведення дентальної імплантації у яких можливе лише після проведення додаткових передімплантаційних кістково-пластичних утручань. При цьому порядок лікування представлено за етапами. За результатами досліджень доведено, що система медичної реабілітації учасників бойових дій із вторинними дефектами зубних рядів потребує більш детального дослідження та вдосконалення.
Dysregulation of ACE (Angiotensin-Converting Enzyme)-2 and Renin-Angiotensin Peptides in SARS-CoV-2 Mediated Mortality and End-Organ Injuries
Authors: Wang Kaiming , Gheblawi Mahmoud , Nikhanj Anish , Munan Matt , MacIntyre Erika , O’Neil Conar , Poglitsch Marko , Colombo Daniele , Del Nonno Franca , Kassiri Zamaneh , Sligl Wendy , Oudit Gavin Y.
Published: November 2021

ACE (angiotensin-converting enzyme)-2 as the target for SARS-CoV-2 also negatively regulates the renin-angiotensin system. Pathological activation of ADAM17 (A disintegrin and metalloproteinase-17) may potentiate inflammation and diminish ACE2-mediated tissue protection through proteolytic shedding, contributing to SARS-CoV-2 pathogenesis. We aim to examine plasma soluble ACE2 and angiotensin profiles in relation to outcomes by enrolling consecutive patients admitted for COVID-19 with baseline blood collection at admission and repeated sampling at 7 days. The primary outcome was 90-day mortality, and secondary outcomes were the incidence of end-organ injuries. Overall, 242 patients were included, the median age was 63 (52–74) years, 155 (64.0%) were men, and 57 (23.6%) patients reached the primary end point. Baseline soluble ACE2 was elevated in COVID-19 but was not associated with disease severity or mortality. In contrast, an upward trajectory of soluble ACE2 at repeat sampling was independently associated with an elevated risk of mortality and incidence of acute myocardial injury and circulatory shock. Similarly, an increase in soluble tumor necrosis factor receptor levels was also associated with adverse outcomes. Plasma Ang I, Ang 1-7 (angiotensin 1–7) levels, and the Ang 1-7/Ang II (angiotensin II) ratio were elevated during SARS-CoV-2 infection related to downregulation of ACE activity at baseline. Moreover, patients having an upward trajectory of soluble ACE2 were characterized by an imbalance in the Ang 1-7/Ang II ratio. The observed dysregulation of ACE2 and angiotensin peptides with disease progression suggest a potential role of ADAM17 inhibition and enhancing the beneficial Ang 1-7/Mas axis to improve outcomes against SARS-CoV-2 infection.
Cardiovascular Family History Increases the Risk of Disease Recurrence After a First Myocardial Infarction
Authors: Wahrenberg Agnes , Kuja‐Halkola Ralf , Magnusson Patrik K. E. , Häbel Henrike , Warnqvist Anna , Hambraeus Kristina , Jernberg Tomas , Svensson Per
Published: November 2021

Background

Family history of atherosclerotic cardiovascular disease (ASCVD) is easily accessible and captures genetic cardiovascular risk, but its prognostic value in secondary prevention is unknown.

Methods and Results

We followed 25 615 patients registered in SWEDEHEART (Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) from their 1‐year revisit after a first‐time myocardial infarction during 2005 to 2013, until December 31, 2018. Data on relatives, diagnoses and socioeconomics were extracted from national registers. The association between family history and recurrent ASCVD was studied with Cox proportional‐hazard regression, adjusting for risk factors and socioeconomics. A family history of ASCVD was defined as hospitalization due to myocardial infarction, angina with coronary revascularization, stroke, or cardiovascular death in ≥1 parent or full sibling, with early‐onset defined as disease‐onset before 55 years in men and 65 in women. The additional discriminatory value of family history to Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention was assessed with Harrell’s C‐index difference and reclassification was studied with continuous net reclassification improvement. Family history of early‐onset ASCVD in ≥1 first‐degree relative was present in 2.3% and was associated with recurrent ASCVD (hazard ratio [HR] 1.31; 95% CI, 1.17–1.47), fully adjusted for risk factors (HR, 1.22; 95% CI, 1.05–1.42). Early‐onset family history improved the discriminatory ability of the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention, with Harrell’s C improving 0.003 points (95% CI, 0.001–0.005) from initial 0.587 (95% CI, 0.576–0.595) and improved reclassification (continuous net reclassification improvement 2.1%,
P
<0.001).

Conclusions

Family history of early‐onset ASCVD is associated with recurrent ASCVD after myocardial infarction, independently of traditional risk factors and improves secondary risk prediction. This may identify patients to target for intensified secondary prevention.
Increased Lung Uric Acid Deteriorates Pulmonary Arterial Hypertension
Authors: Watanabe Takanori , Ishikawa Mariko , Abe Kohtaro , Ishikawa Tomohito , Imakiire Satomi , Masaki Kohei , Hosokawa Kazuya , Fukuuchi Tomoko , Kaneko Kiyoko , Ohtsubo Toshio , Hirano Mayumi , Hirano Katsuya , Tsutsui Hiroyuki
Published: November 2021

Background

Recent studies have demonstrated that uric acid (UA) enhances arginase activity, resulting in decreased NO in endothelial cells. However, the role of lung UA in pulmonary arterial hypertension (PAH) remains uncertain. We hypothesized that increased lung UA level contributes to the progression of PAH.

Methods and Results

In cultured human pulmonary arterial endothelial cells, voltage‐driven urate transporter 1 (URATv1) gene expression was detected, and treatment with UA increased arginase activity. In perfused lung preparations of VEGF receptor blocker (SU5416)/hypoxia/normoxia‐induced PAH model rats, addition of UA induced a greater pressure response than that seen in the control and decreased lung cGMP level. UA‐induced pressor responses were abolished by benzbromarone, a UA transporter inhibitor, or L‐norvaline, an arginase inhibitor. In PAH model rats, induction of hyperuricemia by administering 2% oxonic acid significantly increased lung UA level and induced greater elevation of right ventricular systolic pressure with exacerbation of occlusive neointimal lesions in small pulmonary arteries, compared with nonhyperuricemic PAH rats. Administration of benzbromarone to hyperuricemic PAH rats significantly reduced lung UA levels without changing XOR (xanthine oxidoreductase) activity, and attenuated right ventricular systolic pressure increase and occlusive lesion development. Topiroxostat, a XOR inhibitor, significantly reduced lung XOR activity in PAH rats, with no effects on increase in right ventricular systolic pressure, arterial elastance, and occlusive lesions. XOR‐knockout had no effects on right ventricular systolic pressure increase and arteriolar muscularization in hypoxia‐exposed mice.

Conclusions

Increased lung UA per se deteriorated PAH, whereas XOR had little impact. The mechanism of increased lung UA may be a novel therapeutic target for PAH complicated with hyperuricemia.
Large‐Scale Plasma Protein Profiling of Incident Myocardial Infarction, Ischemic Stroke, and Heart Failure
Authors: Lind Lars , Zanetti Daniela , Ingelsson Martin , Gustafsson Stefan , Ärnlöv Johan , Assimes Themistocles L.
Published: November 2021

Background

We recently reported a link between plasma levels of 2 of 84 cardiovascular disease (CVD)–related proteins and the 3 major CVDs, myocardial infarction, ischemic stroke, and heart failure. The present study investigated whether measurement of almost 10 times the number of proteins could lead to discovery of additional risk markers for CVD.

Methods and Results

We measured 742 proteins using the proximity extension assay in 826 male participants of ULSAM (Uppsala Longitudinal Study of Adult Men) who were free from CVD at the age of 70 years. Cox proportional hazards models were adjusted for age only, as well as all traditional risk factors. During a 12.5‐year median follow‐up (maximal, 22.0 years), 283 incident CVDs occurred. Forty‐one proteins were significantly (false discovery rate <0.05) related to the combined end point of incident CVD, with N‐terminal pro–brain natriuretic peptide as the top finding, while 53 proteins were related to incident myocardial infarction. A total of 13 and 16 proteins were significantly related to incident ischemic stroke and heart failure, respectively. Growth differentiation factor 15, 4‐disulfide core domain protein 2, and kidney injury molecule were related to all of the 3 major CVD outcomes. A lasso selection of 11 proteins improved discrimination of incident CVD by 5.0% (
P
=0.0038).

Conclusions

Large‐scale proteomics seem useful for the discovery of new risk markers for CVD and to improve risk prediction in an elderly population of men. Further studies are needed to replicate the findings in independent samples of both men and women of different ages.
Braiding Braak and Braak: Staging patterns and model selection in network neurodegeneration
Authors: Putra Prama , Thompson Travis B. , Chaggar Pavanjit , Goriely Alain
Published: November 2021

A hallmark of Alzheimer’s disease is the aggregation of insoluble amyloid-beta plaques and tau protein neurofibrillary tangles. A key histopathological observation is that tau protein aggregates follow a structured progression pattern through the brain. Mathematical network models of prion-like propagation have the ability to capture such patterns, but a number of factors impact the observed staging result, thus introducing questions regarding model selection. Here, we introduce a novel approach, based on braid diagrams, for studying the structured progression of a marker evolving on a network. We apply this approach to a six-stage ‘Braak pattern’ of tau proteins, in Alzheimer’s disease, motivated by a recent observation that seed-competent tau precedes tau aggregation. We show that the different modeling choices, from the model parameters to the connectome resolution, play a significant role in the landscape of observable staging patterns. Our approach provides a systematic way to approach model selection for network propagation of neurodegenerative diseases that ensures both reproducibility and optimal parameter fitting.
The discovery of the holotype of Curtia montevidensis (Gentianaceae)
Authors: GOMES-SILVA FRANCIONE , PEREZ LUCIA M. , ALVES MARCCUS
Published: November 2021

N/A
MJO as a Gestalt
Authors: Yano Jun-Ichi
Published: November 2021

Objectively identifying a phenomenon from observation is often difficult. This essay reflects upon this problem from a philosophical perspective by taking the Madden–Julian oscillation (MJO) as an example. I argue that it can be considered as a problem of Gestalt. This concept is introduced by closely following Ludwig Wittgenstein’s two philosophical works, Philosophical Investigations (Philosophische Untersuchungen) and Remarks on the Philosophy of Psychology(Bemerkungen über die Philosophie der Psychologie). Reflections upon the concept of Gestalt suggest why an objective identification of a phenomenon is so difficult. Importantly, the problem should not be reduced to that of “pattern recognition.” Rather a given phenomenon must be considered as a whole, including a question of a driving mechanism.
High-yielding seeds in unyielding environments: Examining the learning process of maize and bean producers in eastern and midwestern Uganda
Authors: Riungu Claris , Maat Harro , Van Den Berg Marrit
Published: November 2021

This paper examines the learning process by which farmers come to a decision to use newly introduced seeds which were promoted through demonstration plots in midwestern and eastern regions of Uganda. Framed as social and material interactions, we investigated the learning process of the demonstration plots using data from focus group discussions, interviews and a survey amongst 983 individuals. The results reveal several constraints that impede learning, resulting in an overall low awareness and adoption of the introduced seeds. Some of the most prominent constraints resulted from the selection of location and demonstration plot host, the distance of agro-dealers, at district headquarters, limited interactions amongst farmers and irregular involvement of farmers in the demonstrations. Moreover, the prominent role of agro-dealers at field days suggests that informing farmers about where to buy seeds was considered more important than explaining farmers how to grow these seeds profitably. This commercial focus of field days and demonstrations plots had negative consequences for the social learning. This paper contributes to the learning and adoption literature by showing that interactions amongst actors can improve or reduce the balance between didactic, social and environmental learning.
Editorial introduction: Design issues and practical questions for demand-oriented seed systems
Authors: Almekinders Conny J.M. , Mausch Kai , Donovan Jason
Published: November 2021

This special issue is a collection of papers that brings together different views on and experiences with seed systems and reflects the breadth of perspectives within CGIAR and beyond. The contributions relate to the major challenges facing seed systems research and development in different contexts and for different crops. One point of agreement among these articles is the need for the development of varieties and the delivery of seeds to be more demand-orientated. This introduction reflects on the implications for CGIAR and affiliated breeding programmes which aim to accelerate varietal uptake and turnover and rely on more effective seed delivery. Here, we outline how the various contributions in this special issue relate to this agenda. We conclude that realism about which farming households can be served by current approaches to seed system development is needed and argue that a wider range of partnerships will be required to broaden the reach of seed systems.
Measuring the COVID-19 Financial Threat to Hospital Markets
Authors: Orlando Anthony W. , Field Robert I.
Published: November 2021

Many hospitals have been straining under the financial stress of treating COVID-19 patients. Those experiencing the greatest strain are in markets burdened with high levels of debt and uncompensated care. We propose a new measure of financial risk in a hospital market, combining both pre-existing financial vulnerability and COVID-19 severity. It reveals the highest concentrations of risk in counties with high poverty, low population density, and high shares of foreign-born and non-White populations. The CARES Act Provider Relief Fund helped many of the hospitals in these regions, but it left many markets with the same overall vulnerability to financial strain from the next health crisis.
Adaptive neural network–based fault estimation for nonlinear systems with actuator faults in simultaneous multiplicative and additive forms
Authors: Zhao Yan , Song Minhang , Huang Xiangguo , Chen Ming
Published: November 2021

Non-linearities and actuator faults often exist in practical systems which may degrade system performance or even lead to catastrophic accidents. In this article, a fault-tolerant compensation control strategy is proposed for a class of non-linear systems with actuator faults in simultaneous multiplicative and additive forms. First, radial basis function neural network is employed to approximate the system non-linearity. The approximation is achieved by only one adaptive parameter, which simplifies the computation burden. Then, by means of the backstepping technique, an adaptive neural controller is developed to cope with the adverse effects brought by the system non-linearity and actuator faults in multiplicative and additive forms. Meanwhile, the proposed control design scheme can guarantee that the considered closed-loop system is stable. The novelty of the article lies in that the system non-linearity, the additive actuator faults, and the multiplicative actuator faults that often exist in practical engineering are catered for simultaneously. Furthermore, compared with some existing works, the approximation of the system non-linearity is achieved by only one adaptive parameter for the purpose of reducing the computation burden. Therefore, its applicability is more general. Finally, a numerical simulation and a comparative simulation are carried out to show the effectiveness of the developed controller.
Early non-EPI DW-MRI after cholesteatoma surgery
Authors: Barbara Maurizio , Covelli Edoardo , Monini Simonetta , Bandiera Giorgio , Filippi Chiara , Margani Valerio , Volpini Luigi , Salerno Gerardo , Romano Andrea , Bozzao Alessandro
Published: November 2021

Objective

Middle ear cholesteatoma may lead to the erosion of the bony structures of the temporal bone, possibly causing intra- and extracranial complications. Surgical treatment is mandatory, and due to possible residual/recurrent disease, the use of reliable diagnostic methods is essential. Our study aimed to evaluate the reliability of non-EPI DW-MRI for the follow-up of cholesteatoma after surgery.

Methods

In a study group including 53 consecutive patients who underwent surgery for cholesteatoma at a tertiary university hospital, an imaging protocol was applied, including non-echo planar diffusion-weighted imaging magnetic resonance (MR) at 1 month after surgery and then at 6 and 12 months after surgery. Based on the combination of preoperative assessment and intraoperative findings, the study group was divided into 3 subgroups: petrous bone (PB) cholesteatoma, complicated cholesteatoma and uncomplicated cholesteatoma. PB cholesteatoma patients were treated by a subtotal petrosectomy, whereas complicated and uncomplicated cholesteatoma patients were treated either by a canal wall up procedure or a retrograde (inside-out) canal wall down technique with bone obliteration technique (BOT).

Results

The results show that patients who had positive findings on non-EPI DW-MRI scans 1 month after surgery consequently underwent revision surgery during which residual cholesteatoma was noted. All the patients who displayed negative findings on non-EPI DWI-MRI scan at 1 month after surgery did not show the presence of a lesion at the 6- and 12-month evaluations. The 6 patients who displayed residual cholesteatoma at the 1-month follow-up presented dehiscence/exposure of the facial nerve canal at the primary surgery, mostly at the level of the labyrinthine segment.

Conclusion

Non-EPI DW-MRI is a useful and reliable tool for follow-up cholesteatoma surgery, and when applied early, as was done in the protocol proposed in the present study, this tool may be used to detect the presence of residual cholesteatoma in some patients, prompting the planning of early revision surgery.
‘I am tired of being afraid’: Emotions and protest participation in Belarus
Authors: Nikolayenko Olena
Published: November 2021

Belarus witnessed a staggering level of mass mobilization in the aftermath of the 2020 fraudulent election and disproportionate use of police force against peaceful protesters. Using the case of anti-government protests in Belarus, this article argues that a confluence of moral and reflex emotions explains an incredibly high level of protest participation in a hard autocracy. Specifically, indignation over the magnitude of electoral malpractices and the intensity of police violence, in congruence with the loss of fear, provides a moral battery for generating and sustaining mass mobilization. It is further argued that a sense of unity within the protest movement mitigates fear of repression and facilitates sustained engagement in protests. Drawing on media reports and protesters’ narratives, the study traces how citizens overcame their fear of state reprisal and took to the street. The article contributes to contentious politics literature by elucidating the role of emotions in shaping mass mobilization.
Mortuary Consumption and the Social Function of Stone Vessels in Early Dynastic Egypt
Authors: Takenouchi Keita
Published: November 2021

This study examines the social functions of stone vessels in Early Dynastic society through a comparison between tomb architecture and the assemblage of stone vessels. The results demonstrated that the more valuable vessels, consisting of special wares and greenish stone vessels, were mostly restricted to high-status tombs in the Memphite and Abydos regions. This hierarchical structure places the king’s and highest officials’ tombs at the top of the hierarchy. Rulers probably distributed stone vessels to elites as part of their political strategy under the administrative institution and system developed since IIIC2. Furthermore, there are formal sets of stone vessels in elite tombs at provincial sites that are close to the vessel assemblage of the ritual list inscribed on funerary slabs during IIID. This suggests that stone vessels were likely brought to provincial areas to promote the offering ritual to local elites in this period. Thus, stone vessels functioned as a political medium for vertical and horizontal integration.
A New Demotic Horoscope from Medinet Habu
Authors: Abbas Eid Nagy Eid
Published: November 2021

The relatively small set of Demotic astrological texts from Medinet Habu may be increased by a newly identified horoscope recorded on an ostracon held at the Cairo Museum. Despite the lack of pertinent data in the official records, the origin of this sherd seems to be certain thanks to some telling palaeographical and textual indications. The date recorded on this potsherd indicates the late first century AD and refers explicitly to the Alexandrian calendar. With regard to the content, it preserves the general format and layout of the Demotic horoscopes on ostraca from Medinet Habu, albeit with some small differences in the type and arrangement of the data. This horoscope leaves out some astronomical data common to other Medinet Habu horoscopes which, along with some other Theban horoscopic ostraca, might confirm a trend among Theban astrologers going from more detailed and complicated compositions to less elaborate and more simplified ones.
Urbanisation at Sannati (c. 300 bc–c. 300 ad): An Early Historic Buddhist Settlement in North Karnataka, India. A Comparative Perspective
Authors: Thakur Hema
Published: November 2021

Urbanisation has been studied almost from the middle of twentieth century by historians, archaeologists, anthropologists, sociologists and city planners who have interpreted it variously. An urban centre would engage with specific functions particularly with regard to the hinterland. In urbanisation comparatively small settlements and simple communities develop into specialised centres and complex societies. As the process of urbanisation is examined from an archaeological or historical viewpoint, the major parameters frequently applied to situate urbanisation are location and size of settlements, large structures, art, writing and standardised medium of exchange. The issue of urbanisation has been studied in detail with respect to Northern India as compared to Deccan and particularly Karnataka. Sannati (Taluk Chittapur, district Gulbarga) in North Karnataka is the main site of investigation. It is a Maurya-Satavahana settlement with some remains belonging to the megalithic Iron Age. Sannati and the nearby settlements of Kanaganahalli are rich in Buddhist structures, sculptures and other antiquities. The author has made an effort to understand if the early historic material culture showed maturity when compared with the antecedent cultures. How did the external powers, such as Mauryas and the Satavahanas influence local development? Did the socio-political order meet the benchmarks of urbanisation? The author in this study has tried to locate urban contours in North Karnataka, especially at Sannati even when compared with other urban landscapes in northern India and the Deccan.
Image processing method for delamination and fiber pull-out assessment during drilling of natural fiber composites
Authors: Abdul Kudus Muhammad Helmi , Ratnam Mani Maran , Md Akil Hazizan
Published: November 2021

Natural fiber-reinforced composites are promising alternative materials in the manufacture of modern moderate-to-high-technology products. However, their heterogeneous structure causes processing defects uncommon with metallic parts. Drilling of composites is an essential machining process to facilitate assembly and fastening of composite components. The occurrence of delamination damage around the drilled hole and fiber pull-out within the hole are critical factors that affect the performance of these parts when assembled. A new image processing method using digital scanning and tracing for characterizing delamination and fiber pull-out induced by drilling has been developed to address the limitations in the existing methods of quantifying drilled hole qualities. The capability of the proposed method as a delamination and fiber pull-out assessment tool was verified using simulated and real images of drilled holes. The method was also used to investigate the effect of drilling parameters on delamination and fiber pull-out in jute reinforced epoxy composite produced via resin transfer molding. The results show that drill bit diameter, feed rate, and spindle speed have varying effects on both delamination areas and fiber pull-out within the drilled hole.
Do environmental policy and innovation improve carbon productivity? Evidence from the Korean Emission Trading Scheme
Authors: Mo Jung Youn
Published: November 2021

This study investigates the relationship among technology innovation, emission trading schemes, and carbon productivity based on data from firms participating in the Korean Emission Trading Scheme. First, the total factor carbon productivity based on stochastic frontier analysis is estimated by industry and it is confirmed that changes in carbon productivity vary by industry. Based on the estimated carbon productivity, panel data analysis is conducted to determine the effects of innovation and environmental policy on carbon productivity. The results show that R&D investment and environmental policy play an important role in promoting carbon productivity. In this study, the factors affecting carbon productivity are also analyzed by industry. Comparative analysis across industries confirms that factors affecting environmental performance vary by industry. Innovation does not significantly affect carbon productivity in assembling industries, but in the process industry, R&D investment plays an important role in increasing environmental performance.