bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictability effects and parafoveal processing of compound words in natural Chinese reading
Authors: Cui Lei , Zang Chuanli , Xu Xiaochen , Zhang Wenxin , Su Yuhan , Liversedge Simon P
Published: September 2021

We report a boundary paradigm eye movement experiment to investigate whether the predictability of the second character of a two-character compound word affects how it is processed prior to direct fixation during reading. The boundary was positioned immediately prior to the second character of the target word, which itself was either predictable or unpredictable. The preview was either a pseudocharacter (nonsense preview) or an identity preview. We obtained clear preview effects in all conditions, but more importantly, skipping probability for the second character of the target word and the whole target word from pretarget was greater when it was predictable than when it was not predictable from the preceding context. Interactive effects for later measures on the whole target word (gaze duration and go-past time) were also obtained. These results demonstrate that predictability information from preceding sentential context and information regarding the likely identity of upcoming characters are used concurrently to constrain the nature of lexical processing during natural Chinese reading.
Redesigning the exploration of semantic dynamics: SSD account in light of regression design
Authors: Mišić Ksenija , Filipović Đurđević Dušica
Published: September 2021

The Semantic Settling Dynamics model postulated that the seemingly inconsistent effects of lexical ambiguity are, in fact, a systematic manifestation of the specific dynamics that arise as a consequence of the amount of time spent in processing. The model has thus far been tested by prolonging lexical decision and comparing homonymous, polysemous, and unambiguous words in a factorial design. Here, we kept the strategy of task manipulation but tested the model by using continuous measures as indices of the level of lexical ambiguity and their slopes as indices of the effect size. We expressed the size of the polysemy effect as the slope of the effect of entropy of sense probability distribution and the size of the homonymy effect as the redundancy of sense probability distribution. Comparing lexical decision tasks with the shorter and longer time spent in processing, we observed the predicted decrease in the effect of the polysemy level as well as the predicted increase in the effect of homonymy level.
Sacrificial causalities of nuclear weapons: Takashi Nagai and Albert Wohlstetter
Authors: DeMars William E
Published: September 2021

After the U.S. dropped atomic bombs on Hiroshima and Nagasaki in Japan in 1945, both nations experienced a profound need for a new and encompassing story of what it meant to be Japanese, and to be American, in the permanent nuclear age. This article is a thought experiment to juxtapose the writings and personas of two people who helped their respective societies answer those needs and questions during the early Cold War: Takashi Nagai—medical radiologist, and survivor of the American atomic bombing of Nagasaki, and Albert Wohlstetter—leading American civilian nuclear strategist for the RAND Corporation in the 1950s. Using a combination of mythopeic analysis, biography and illuminative juxtaposition, the study discovers surprising similarities and analogies between the two cases. They each enact and propose interesting variations of sacrificial causalities—claims that human nuclear sacrifices past or promised can bring peace by deterrence now or peace by abolition soon enough. This is an important study now, as both Japan’s nuclear pacifism and the American nuclear umbrella in Northeast Asia are coming under more severe questioning than perhaps ever before.
Early perception, behavior, knowledge, and preventive practices related to COVID-19 among Palestinians
Authors: Salameh Basma Salim , Basha Sami , Abdallah Jihad , Basha Walid
Published: September 2021

It is necessary to understand early perception, behavior, and knowledge of coronavirus disease 2019 (COVID-19) and preventive practices in relation to suggested policies and information accessible to the Palestinian population during the early stages of the pandemic. The aim of this research is to contribute to this understanding for the purpose of affecting future practical preventive policies that can be implemented and adapted in Palestine in order to shape a new reflective practices model to face any future epidemic crisis of any type. A cross-sectional design was used to conduct the study over 3 weeks in April 2020 and an online survey was disseminated in all areas of Palestine. A total of 1040 responses were collected from persons who were over 18 years of age. A high level of knowledge related to COVID-19 was found, including symptoms and characteristics of the virus, prevention practices, and at-risk groups. Respondents believe that they are more susceptible to influenza than COVID-19 and more likely to be infected by the influenza virus than the COVID-19 virus but expect that infection of influenza would be less severe than infection of COVID-19. Respondents were more inclined to find COVID-19 worrying and stressful than they were to find it fear-inducing. Around two-thirds of respondents believe that different types of COVID-19-related conspiracy theories are true to some degree. Going forward, it is crucial and essential to provide basic awareness among large populations around diseases, which can contribute to positively influencing people’s knowledge and attitudes and their perception toward such diseases and combat conspiracy theories.
Visioning the future of health promotion
Authors: Kickbusch Ilona
Published: September 2021

COVID-19 has shown us clearly that the world must commit to a transformative approach that promotes health and wellbeing. Living in the Anthropocene – an epoch defined by human impact on our ecosystems – moves us into unknown territory. The challenge is to find a way of living that aims to meet the needs of all people within the means of the living planet. We will require foresight, agility and resilience to be well prepared. The global risks we face are enormous and they are interconnected – yet the opportunity to accelerate change for the better is extraordinary as well. We have models, knowledge and technologies at our disposal that could significantly improve health and wellbeing and create fairer and more sustainable societies – yet they have not been used widely to serve the public purpose and to address inequities.
A connected community response to COVID-19 in Toronto
Authors: Morgan Garrett T. , Poland Blake , Jackson Suzanne F. , Gloger Anne , Luca Sarah , Lach Norene , Rolston Imara Ajani
Published: September 2021

In this commentary, we describe initial learnings from a community-based research project that explored how the relational space between residents and formal institutions in six marginalised communities in Toronto, Ontario, Canada impacted grassroots responses to the health and psycho-social stresses that were created and amplified by the coronavirus disease 2019 (COVID-19) pandemic. Our research found that grassroots community leaders stepped up to fill the gaps left by Toronto’s formal public health and emergency management systems and were essential for mitigating the psycho-social and socioeconomic impacts of the pandemic that exacerbated pre-existing inequities and systemic failures. We suggest that building community resilience in marginalised communities in Toronto can embody health promotion in action where community members, organisational, institutional and government players create the social infrastructure necessary to build on local assets and work together to promote health by strengthening community action, advocating for healthy public policy and creating supportive environments.
Asenapine: an atypical antipsychotic with atypical formulations
Authors: Musselman Meghan , Faden Justin , Citrome Leslie
Published: September 2021

Asenapine is a second-generation (atypical) antipsychotic medication not available in a pill that can be swallowed; rather, it is commercialized in sublingual and transdermal formulations. This is a consequence of extensive first-pass metabolism if ingested. The sublingual formulation is approved in many jurisdictions for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder and is available generically. The efficacy profile is well characterized in a number of clinical trials, including an off-label use for the management of agitation. Obstacles to its use include food and drink restrictions, twice-daily dosing and adverse effects such as dysgeusia (distorted, altered, or unpleasant taste) and oral hypoesthesia (numbness). Transdermal asenapine was approved by the US Food and Drug Administration in 2019 for the treatment of schizophrenia in adults. Efficacy was established in a registrational study examining acutely ill inpatients with schizophrenia. The patch needs to changed once daily. Obstacles to its use include the potential for skin reactions such as erythema and pruritis, and being a branded product, it is more costly than other options. This is a narrative review of the chemistry and pharmacokinetics/pharmacodynamics of asenapine, as well as summarizing the efficacy and tolerability of both sublingual and transdermal asenapine, and its possible place in treatment.
The effect of a large dose of intravenous immunoglobulin on general paresis of the insane
Authors: Qingqing Chen , Dongliang Liu , Qingqing Sang , Daoqian Sang
Published: September 2021

General paresis of the insane (GPI) remains the form of neurosyphilis most closely associated with dementia, even after the advent of penicillin. Penicillin remains the top treatment choice for syphilis, but treatment failure is not rare. Although the neurological symptoms of GPI can be alleviated by antibiotic treatment, mental symptoms may continue. A 60-year-old man was admitted to hospital due to rapidly progressive dementia. He was diagnosed as GPI. With the patient’s informed consent, we treated him with a large dose of intravenous immunoglobulin (IVIG) (0.4 g/kg/day) for 5 days, as well as penicillin (24 million units daily divided into six doses) for 14 days. A near-immediate improvement in his emotions and orientation occurred on the 17th day in hospital. The patient made an excellent recovery 6 weeks after treatment, his psychotic and mood symptoms improved significantly. Therefore, we hypothesize that patients with GPI treated with IVIG and penicillin G would have better outcomes than those treated with penicillin G alone. IVIG may be introduced as a necessary treatment for GPI.
Increased Comorbidity Burden Among Hip Fracture Patients During the COVID-19 Pandemic in New York City
Authors: LeBrun Drake G. , Konnaris Maxwell A. , Ghahramani Gregory C. , Premkumar Ajay , DeFrancesco Chris J. , Gruskay Jordan A. , Dvorzhinskiy Aleksey , Sandhu Milan S. , Goldwyn Elan M. , Mendias Christopher L , Ricci William M.
Published: September 2021

Background

The coronavirus disease 19 (COVID-19) pandemic had a devastating effect on New York City in the spring of 2020. Several global reports suggested worse early outcomes among COVID-positive patients with hip fractures. However, there is limited data comparing baseline comorbidities among patients treated during the pandemic relative to those treated in non-pandemic conditions.

Materials and Methods

A multicenter retrospective cohort study was performed at two Level 1 Trauma centers and one orthopedic specialty hospital to assess demographics, comorbidities, and outcomes among 67 hip fracture patients treated (OTA/AO 31, 32.1) during the peak of the COVID-19 pandemic in New York City (March 20, 2020 to April 24, 2020), including 9 who were diagnosed with COVID-19. These patients were compared to a cohort of 76 hip fracture patients treated 1 year prior (March 20, 2019 to April 24, 2019). Baseline demographics, comorbidities, treatment characteristics, and respiratory symptomatology were evaluated. The primary outcome was inpatient mortality.

Results

Relative to patients treated in 2019, patients with hip fractures during the pandemic had worse Charlson Comorbidity Indices (median 5.0 vs 6.0, P = .03) and American Society of Anesthesiologists (ASA) scores (mean 2.4 vs 2.7, P = .04). Patients during the COVID-19 pandemic were more likely to have decreased ambulatory status ( P<.01) and a smoking history ( P = .04). Patients in 2020 had longer inpatient stays (median 5 vs 7 days, P = .01), and were more likely to be discharged home (61% vs 9%, P<.01). Inpatient mortality was significantly increased during the COVID-19 pandemic (12% vs 0%, P = .002).

Conclusions

Patients with hip fractures during the COVID-19 pandemic had worse comorbidity profiles and decreased functional status compared to patients treated the year prior. This information may be relevant in negotiations regarding reimbursement for cost of care of hip fracture patients with COVID-19, as these patients may require more expensive care.
Ethnic Distinctions, Legal Connotations: Chinese Patterns of Boundary Making and Crossing
Authors: Lee Byung-Ho
Published: September 2021

This study analyzes, from a comparative and historical perspective, the clash between state statutory law and native customary law and the consequential effects of that rivalry on ethno-legal categories. It adopts a long-term perspective on Chinese society, with a particular focus on its history over the last three centuries. Although the imperial Chinese state had a centralized legal code, many non-Han subjects followed different legal standards and systems. Such conditions became the basis of legal pluralism and the structural constraint for full-fledged legal uniformity. It is argued that state-imposed ethnic categories in China have been institutionalized to determine those who should be protected, or even privileged, by their own native law. This is especially true during the alien dynasties of conquest, which purposely emphasized the principle of personal law to preserve legal prerogatives of ruling ethnicity. Similarly, indigenes on the frontier carried a variety of legal exemptions on grounds of the principle of territorial law. Such conditions could leave room for individual agency and provide incentives for both acculturated Han settlers and sinicized indigenes to claim native status. Several examples, including an 18th-century homicide case in China’s southwestern frontier, substantiate how individuals manipulated their ethnicity for their self-advantage and how these behaviors complicated the personality and territoriality principles of imperial law. In this sense, ethnic law served as an institutionalized distillation of ethnic group boundaries, which were realigned by shifts in self-identity. The legacy of China’s imperial practices of particularistic jural relations continues today.
Coaching in Complexity: Lessons Learned Investigating Implementation of Interventions in High Schools
Authors: Kucharczyk Suzanne , Szidon Kate , Hall Laura J.
Published: September 2021

High schools hold great potential as contexts within which educators implement evidence-based practices shown to change post-school outcomes for youth with autism spectrum disorder (ASD). Unfortunately, educators feel unprepared to use transition and disability-focused evidence-based practices. Coaching, as an essential feature of effective professional development, is an important process for supporting educators in their development of competencies for use of these practices. To inform the use of coaching in complex high school settings, the model used by the Center on Secondary Education for Students With ASD to implement a comprehensive package of disability- and transition-focused interventions in 30 schools is described and coaching data analyzed to offer lessons learned for developing professional development supports for secondary school practitioners. Limitations and implications for research and practice are discussed.
Nodular Regenerative Hyperplasia of the Liver in Rheumatic Disease: Cases and Review of the Literature
Authors: Jain Prarthana , Patel Sagar , Simpson Heather N. , Silver Richard M. , Lewin David N. , Campbell Ruth C. , Guimaraes Marcelo , Silver Katherine C.
Published: September 2021

Nodular regenerative hyperplasia (NRH) is a rare disease that is characterized by benign transformation of the hepatic parenchyma into small nodules with little to no fibrosis. Nodular regenerative hyperplasia is a cause of noncirrhotic portal hypertension. Symptoms can range from asymptomatic disease to more serious complications of portal hypertension such as esophageal varices and ascites. Nodular regenerative hyperplasia has been described in association with a variety of different rheumatologic, hematologic, and oncologic diseases, as well as in immune deficiency states and with exposures to certain toxins. Diagnosis is made by histology, and the treatment involves addressing the underlying disease. The first description of this rare disease was actually described in a patient with rheumatoid arthritis, neutropenia, and splenomegaly (Felty’s Syndrome). We describe 2 cases of NRH associated with underlying rheumatic disorders, in one of which NRH was actually the presenting feature of the patient’s underlying autoimmune condition. Subsequently, we provide a brief review of the literature of NRH in autoimmune disease with respect to epidemiology, cause, clinical manifestations, diagnosis, and treatment.
How to write a guideline: a proposal for a manuscript template that supports the creation of trustworthy guidelines
Authors: Nieuwlaat Robby , Wiercioch Wojtek , Brozek Jan L. , Santesso Nancy , Kunkle Robert , Alonso-Coello Pablo , Anderson David R. , Bates Shannon M. , Dahm Philipp , Iorio Alfonso , Lim Wendy , Lyman Gary H. , Middeldorp Saskia , Monagle Paul , Mustafa Reem A. , Neumann Ignacio , Ortel Thomas L. , Rochwerg Bram , Vesely Sara K. , Witt Daniel M. , Cuker Adam , Schünemann Holger J.
Published: September 2021

Trustworthy health guidelines should provide recommendations, document the development process, and highlight implementation information. Our objective was to develop a guideline manuscript template to help authors write a complete and useful report. The McMaster Grading of Recommendations Assessment, Development and Evaluation Centre collaborated with the American Society of Hematology (ASH) to develop guidelines for the management of venous thromboembolism. A template for reporting the guidelines was developed based on prior approaches and refined using input from other key stakeholders. The proposed guideline manuscript template includes: (1) title for guideline identification, (2) abstract, including a summary of key recommendations, (3) overview of all recommendations (executive summary), and (4) the main text, providing sufficient detail about the entire process, including objectives, background, and methodological decisions from panel selection and conflict-of-interest management to criteria for updating, as well as supporting information, such as links to online (interactive) tables. The template further allows for tailoring to the specific topic, using examples. Initial experience with the ASH guideline manuscript template was positive, and challenges included drafting descriptions of recommendations involving multiple management pathways, tailoring the template for a specific guideline, and choosing key recommendations to highlight. Feedback from a larger group of guideline authors and users will be needed to evaluate its usefulness and refine. The proposed guideline manuscript template is the first detailed template for transparent and complete reporting of guidelines. Consistent application of the template may simplify the preparation of an evidence-based guideline manuscript and facilitate its use.
Methods of induction of labor and women’s experience: a population-based cohort study with mediation analyses
Authors: Blanc-Petitjean Pauline , Dupont Corinne , Carbonne Bruno , Salomé Marina , Goffinet François , Ray Camille Le ,   for the MEDIP study group, Crenn-Hebert Catherine , Gaudineau Adrien , Perrotte Frédérique , Raynal Pierre , Clouqueur Elodie , Beucher Gaël , Deneux-Tharaux Catherine , Ancel Pierre-Yves
Published: September 2021

Background

Negative childbirth experience may affect mother wellbeing and health. However, it is rarely evaluated in studies comparing methods of induction of labor (IoL).

Aim

To compare women’s experience of IoL according to the method, considering the mediating role of interventions and complications of delivery.

Methods

We used data from the MEDIP prospective population-based cohort, including all women with IoL during one month in seven French perinatal networks. The experience of IoL, assessed at 2 months postpartum, was first compared between cervical ripening and oxytocin, and secondarily between different cervical ripening methods. Mediation analyses were used to measure the direct and indirect effects of cervical ripening on maternal experience, through delivery with interventions or complications.

Findings

The response rate was 47.8% (n = 1453/3042). Compared with oxytocin (n = 541), cervical ripening (n = 910) was associated less often with feelings that labor went ‘as expected’ (adjusted risk ratio for the direct effect 0.78, 95%CI [0.70–0.88]), length of labor was ‘acceptable’ (0.76[0.71–0.82]), ‘vaginal discomfort’ was absent (0.77[0.69–0.85]) and with lower global satisfaction (0.90[0.84–0.96]). Interventions and complications mediated between 6 and 35% of the total effect of cervical ripening on maternal experience. Compared to the dinoprostone insert, maternal experience was not significantly different with the other prostaglandins. The balloon catheter was associated with less pain.

Discussion

Cervical ripening was associated with a less positive experience of childbirth, whatever the method, only partly explained by interventions and complications of delivery.

Conclusion

Counselling and support of women requiring cervical ripening might be enhanced to improve the experience of IoL.
The different risk factors for isolated diastolic hypertension and isolated systolic hypertension: a national survey
Authors: Xie Kun , Gao Xiufang , Bao Liwen , Shan Ying , Shi Haiming , Li Yong
Published: September 2021

Background

Hypertension is highly prevalent and is one of the modifiable risk factors for cardiovascular outcomes. Isolated diastolic hypertension (IDH), however, tends to be ignored due to insufficient recognition. We sought to depict the clinical manifestation of IDH and isolated systolic hypertension (ISH) to find a more efficient way to improve the management.

Methods

Patients with primary hypertension aged over 18 years were investigated from all over the country using convenience sampling during 2017–2019. IDH was defined as systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) ≥90 mmHg. ISH was defined as SBP ≥ 140 mmHg and DBP < 90 mmHg.

Results

A total of 8548 patients were screened, and 8475 participants were included. The average age was 63.67 ± 12.78 years, and males accounted for 54.4%. Among them, 361 (4.3%) had IDH, and 2096 had ISH (24.7%). Patients with IDH (54.84 ± 13.21 years) were much younger. Aging turned out to be negatively associated with IDH but positively associated with ISH. Multivariate logistic regression analysis showed BMI was a significant risk factor for IDH (OR 1.30, 95%CI 1.05–1.61, p = 0.018), but not for ISH (OR 1.05, 95%CI 0.95–1.16, p = 0.358). Moreover, smoking was significantly associated with IDH (OR 1.36, 95%CI 1.04–1.78, p = 0.026) but not with ISH (OR 1.04, 95%CI 0.90–1.21, p = 0.653).

Conclusions

Patients with IDH were much younger, and the prevalence decreased with aging. BMI and smoking were remarkably associated with IDH rather than ISH. Keeping fit and giving up smoking might be particularly efficient in the management of young patients with IDH.

Trial registration

NCT03862183, retrospectively registered on March 5, 2019.
Investigating geographical variation in the use of mental health services by area of England: a cross-sectional ecological study
Authors: Maconick Lucy , Sheridan Rains Luke , Jones Rebecca , Lloyd-Evans Brynmor , Johnson Sonia
Published: September 2021

Background

There is evidence of geographical variation in the use of mental health services in the UK and in international settings. It is important to understand whether this variation reflects differences in the prevalence of mental disorders, or if there is evidence of variation related to other factors, such as population socioeconomic status and access to primary care services.

Methods

This is a cross-sectional ecological study using Public Health England data. The unit of analysis was the population served by clinical commissioning groups (CCGs), National Health Service (NHS) catchment areas. The analysis explored associations between area characteristics and the number of people in contact with mental health services using regression modelling. Explanatory variables included age, gender, prevalence of severe mental illness (SMI), prevalence of common mental disorder (CMD), index of multiple deprivation (IMD), unemployment, proportion of the population who are Black and Minority Ethnic (BAME), population density, access to and recovery in primary care psychological therapies. Unadjusted results are reported, as well as estimates adjusted for age, prevalence of CMD and prevalence of SMI.

Results

The populations of 194 CCGs were included, clustered within 62 trusts (NHS providers of mental health services). The number of people in contact with mental health services showed wide variation by area (range from 1131 to 5205 per 100,000 population). Unemployment (adjusted IRR 1.11; 95% CI 1.05 to 1.17; p < 0.001) and deprivation (adjusted IRR 1.02 95% CI 1.01 to 1.04; p < 0.001) were associated with more people being in contact with mental health services. Areas with a higher proportion of the population who are BAME (IRR 0.95 95% CI 0.92 to 0.99 p = 0.007) had lower service use per 100,000 population. There was no evidence for association with access to primary care psychological therapies.

Conclusions

There is substantial variation in the use of mental health services by area of England. Social factors including deprivation, unemployment and population ethnicity continued to be associated with the outcome after controlling for the prevalence of mental illness. This suggests that there are factors that influence the local population use of mental health services in addition to the prevalence of mental disorder.
Phylogeography and population differentiation in Hepatozoon canis (Apicomplexa: Hepatozoidae) reveal expansion and gene flow in world populations
Authors: Vásquez-Aguilar Antonio Acini , Barbachano-Guerrero Arturo , Angulo Diego F. , Jarquín-Díaz Víctor Hugo
Published: September 2021

Background

Hepatozoon canis is a protozoan transmitted to dogs and other wild carnivores by the ingestion of ticks containing mature oocysts and is considered the principal cause of canine hepatozoonosis in the world. Here, we examined ribosomal RNA 18S gene sequence variation to determine the genetic differences and phylogeographic diversity of H. canis from various geographical areas around the world.

Methods

We used 550 publicly available sequences of H. canis from 46 countries to assess haplotype relationships, geographical structure, genetic diversity indices, and relationships among populations. We performed neutrality tests and pairwise comparisons of fixation index (FST) values between groups and pairwise comparisons of FST values between populations. To determine whether populations are structured, analyses of molecular variance (AMOVAs) and spatial analysis of molecular variance (SAMOVA) were performed.

Results

The dataset of H. canis yielded 76 haplotypes. Differentiation among populations indicated that there is no phylogeographical structure (GST = 0.302 ± 0.0475). Moreover, when samples were grouped by continents a significant FST was obtained, meaning that populations were genetically differentiated. The AMOVA showed that 57.4% of the genetic variation was explained by differences within populations when all locations were treated as a single group and revealed that there is no population structure when populations are grouped into two, three, and four groups (FCT, p > 0.05), suggesting that dispersal between populations is high. SAMOVA revealed significant FCT values for groups K = 5. The Tajima’s D and Fu’s Fs show that populations have undergone recent expansion, and the mismatch distribution analysis showed population expansion (multimodal distribution).

Conclusions

The current molecular data confirmed that H. canis does not show phylogeographic or population structure. The haplotypes exhibit low genetic differentiation, suggesting a recent expansion due to gene flow among populations. These results provide pivotal information required for future detailed population genetic analysis or to establish control strategies of this parasite.

Graphical abstract
MicroRNA-497 induced by Clonorchis sinensis enhances the TGF-β/Smad signaling pathway to promote hepatic fibrosis by targeting Smad7
Authors: Zhou Qian-Yang , Yang Hui-Min , Liu Ji-Xin , Xu Na , Li Jing , Shen Li-Ping , Zhang Yu-Zhao , Koda Stephane , Zhang Bei-Bei , Yu Qian , Chen Jia-Xu , Zheng Kui-Yang , Yan Chao
Published: September 2021

Background

Various stimuli, including Clonorchis sinensis infection, can cause liver fibrosis. Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) with massive production of extracellular matrix (ECM). Our previous study showed that the TGF-β1-induced Smad signaling pathway played a critical role in the activation of HSCs during liver fibrosis induced by worm infection; however, the mechanisms that modulate the TGF-β/Smad signaling pathway are still poorly understood. Accumulating evidence demonstrates that miRNAs act as an important regulator of activation of HSCs during liver fibrosis.

Methods

The target of miR-497 was determined by bioinformatics analysis combined with a dual-luciferase activity assay. LX-2 cells were transfected with miR-497 inhibitor and then stimulated with TGF-β1 or excretory/secretory products of C. sinensis (CsESPs), and activation of LX-2 was assessed using qPCR or western blot. In vivo, the mice treated with CCl4 were intravenously injected with a single dose of adeno-associated virus serotype 8 (AAV8) that overexpressed anti-miR-497 sequences or their scramble control for 6 weeks. Liver fibrosis and damage were assessed by hematoxylin and eosin (H&E) staining, Masson staining, and qPCR; the activation of the TGF-β/Smad signaling pathway was detected by qPCR or western blot.

Results

In the present study, the expression of miR-497 was increased in HSCs activated by TGF-β1 or ESPs of C. sinensis. We identified that Smad7 was the target of miR-497 using combined bioinformatics analysis with luciferase activity assays. Transfection of anti-miR-497 into HSCs upregulated the expression of Smad7, leading to a decrease in the level of p-Smad2/3 and subsequent suppression of the activation of HSCs induced by TGF-β1 or CsESPs. Furthermore, miR-497 inhibitor delivered by highly-hepatotropic (rAAV8) inhibited TGF-β/smads signaling pathway by targeting at Smad7 to ameliorate CCL4-induced liver fibrosis.

Conclusions

The present study demonstrates that miR-497 promotes liver fibrogenesis by targeting Smad7 to promote TGF-β/Smad signaling pathway transduction both in vivo and in vitro, which provides a promising therapeutic strategy using anti-miR-497 against liver fibrosis.

Graphical Abstract
Migrated fish bone into the neck: a case report
Authors: Thuduvage Vasanthika Sanjeewanie
Published: September 2021

Background

Impaction of foreign body is a common condition presented to ear, nose, and throat department among Asian population. The commonest foreign body seen among this population has been documented as fish bone. Fish bone can migrate to lateral neck space or related organs around the neck and chest. By presenting this case report, we aim to emphasize the importance of taking proper history and make clinicians aware of the possibility of a fish bone migrating into different spaces. This will help to prevent diagnosis delay leading to complications due to migrated fish bone.

Case presentation

A 50-year-old female Sinhalese patient presented to ear, nose, and throat department with right-sided neck pain for 2 days, who had a history of suspected fish bone impaction a few days ago that subsided without any investigations or treatments. She did not have any symptoms related to throat, and neck examination showed mild swelling and tenderness. Computer tomography revealed a migrated fish bone into the lateral neck close to carotid artery, and the fish bone was removed by neck exploration under general anesthesia without any complications.

Conclusion

In conclusion, migrated fish bone should be suspected if patient is having persistent symptoms mainly in the neck without having difficulty swallowing and who gives a history of fish bone impaction and having negative laryngoscopic examination. Proper history taking is very important in the assessment of these patients to prevent misdiagnosis of the condition. Clinicians should aware that migrated fish bones are not uncommon and that early suspicion can prevent later diagnosis and complications.
Targeted strategies for the management of wildlife diseases: the case of brucellosis in Alpine ibex
Authors: Lambert Sébastien , Thébault Anne , Rossi Sophie , Marchand Pascal , Petit Elodie , Toïgo Carole , Gilot-Fromont Emmanuelle
Published: September 2021

The management of infectious diseases in wildlife reservoirs is challenging and faces several limitations. However, detailed knowledge of host–pathogen systems often reveal heterogeneity among the hosts’ contribution to transmission. Management strategies targeting specific classes of individuals and/or areas, having a particular role in transmission, could be more effective and more acceptable than population-wide interventions. In the wild population of Alpine ibex (Capra ibex—a protected species) of the Bargy massif (French Alps), females transmit brucellosis (Brucella melitensis) infection in ~90% of cases, and most transmissions occur in the central spatial units (“core area”). Therefore, we expanded an individual-based model, developed in a previous study, to test whether strategies targeting females or the core area, or both, would be more effective. We simulated the relative efficacy of realistic strategies for the studied population, combining test-and-remove (euthanasia of captured animals with seropositive test results) and partial culling of unmarked animals. Targeting females or the core area was more effective than untargeted management options, and strategies targeting both were even more effective. Interestingly, the number of ibex euthanized and culled in targeted strategies were lower than in untargeted ones, thus decreasing the conservation costs while increasing the sanitary benefits. Although there was no silver bullet for the management of brucellosis in the studied population, targeted strategies offered a wide range of promising refinements to classical sanitary measures. We therefore encourage to look for heterogeneity in other wildlife diseases and to evaluate potential strategies for improving management in terms of efficacy but also acceptability.
Recent aspects of ketogenic diet in neurological disorders
Authors: Kwon Hye Eun , Kim Heung Dong
Published: September 2021

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet, in which fat is used as the primary energy source through the production of ketone bodies (KBs) in place of glucose. The KD was formally introduced in 1921 to mimic the biochemical changes associated with fasting and gained recognition as a potent treatment for pediatric epilepsy in the mid-1990s. The clinical and basic scientific knowledge that supports the anti-seizure efficacy, safety, and feasibility of using the KD in patients with epilepsy is huge. Additionally, the International Ketogenic Diet Study Group’s consensus guidelines provide practical information in 2009 and 2018. The KD is a broad-spectrum therapy for drug resistant epilepsy and is gaining attention as a potential therapy for other neurological disorders. This article will review recent aspects on the use of the KD, including its mechanisms of action, KD alternatives, expanding its use across different age groups and regions, its use as a treatment for other neurologic disorders, and future research subjects.
Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma
Authors: Sonneveld Pieter , Dimopoulos Meletios A. , Beksac Meral , van der Holt Bronno , Aquino Sara , Ludwig Heinz , Zweegman Sonja , Zander Thilo , Zamagni Elena , Wester Ruth , Hajek Roman , Pantani Lucia , Dozza Luca , Gay Francesca , Cafro AnneMaria , De Rosa Luca , Morelli Annamaria , Gregersen Henrik , Gulbrandsen Nina , Cornelisse Petra , Troia Rosella , Oliva Stefania , van de Velden Vincent , Wu KaLung , Ypma Paula F. , Bos Gerard , Levin Mark-David , Pour Luca , Driessen Christoph , Broijl Annemiek , Croockewit Alexandra , Minnema Monique C. , Waage Anders , Hveding Cecilie , van de Donk Niels W. C. J. , Offidani Massimo , Palumbo Giuseppe A. , Spencer Andrew , Boccadoro Mario , Cavo Michele
Published: September 2021

PURPOSE

To address the role of consolidation treatment for newly diagnosed, transplant eligible patients with multiple myeloma in a controlled clinical trial.

PATIENTS AND METHODS

The EMN02/HOVON95 trial compared consolidation treatment with two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) or no consolidation after induction and intensification therapy, followed by continuous lenalidomide maintenance. Primary study end point was progression-free survival (PFS).

RESULTS

Eight hundred seventy-eight eligible patients were randomly assigned to receive VRD consolidation (451 patients) or no consolidation (427 patients). At a median follow-up of 74.8 months, median PFS with adjustment for pretreatment was prolonged in patients randomly assigned to VRD consolidation (59.3 v 42.9 months, hazard ratio [HR] = 0.81; 95% CI, 0.68 to 0.96; P = .016). The PFS benefit was observed across most predefined subgroups, including revised International Staging System (ISS) stage, cytogenetics, and prior treatment. Revised ISS3 stage (HR, 2.00; 95% CI, 1.41 to 2.86) and ampl1q (HR, 1.67; 95% CI, 1.37 to 2.04) were significant adverse prognostic factors. The median duration of maintenance was 33 months (interquartile range 13-86 months). Response ≥ complete response (CR) after consolidation versus no consolidation before start of maintenance was 34% versus 18%, respectively ( P < .001). Response ≥ CR on protocol including maintenance was 59% with consolidation and 46% without ( P < .001). Minimal residual disease analysis by flow cytometry in a subgroup of 226 patients with CR or stringent complete response or very good partial response before start of maintenance demonstrated a 74% minimal residual disease–negativity rate in VRD-treated patients. Toxicity from VRD was acceptable and manageable.

CONCLUSION

Consolidation treatment with VRD followed by lenalidomide maintenance improves PFS and depth of response in newly diagnosed patients with multiple myeloma as compared to maintenance alone.
Association of MAFLD With Diabetes, Chronic Kidney Disease, and Cardiovascular Disease: A 4.6-Year Cohort Study in China
Authors: Liang Yebei , Chen Hongli , Liu Yuexing , Hou Xuhong , Wei Li , Bao Yuqian , Yang Chunguang , Zong Geng , Wu Jiarui , Jia Weiping
Published: September 2021

Context

In 2020, the terminology of metabolic dysfunction–associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD).

Objectives

This work aimed to investigate the prevalence and incidence of MAFLD and evaluate its effects on incident extrahepatic diseases.

Methods

A total of 6873 individuals, with a 4.6-year follow-up, were included in this study. Associations of MAFLD and NAFLD with diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD) were examined using logistic regression and Cox proportional hazards models.

Results

The prevalence of NAFLD and MAFLD was 40.3% (95% CI, 39.2%-41.5%) and 46.7% (95% CI, 45.6%-47.9%), respectively. Additionally, 321 (4.7%) and 156 (2.3%) participants had MAFLD with excessive alcohol consumption and hepatitis B virus (HBV) infection. During the follow-up period, the incidence of NAFLD and MAFLD was 22.7% (95% CI, 21.3%-24.0%) and 27.0% (95% CI, 25.5%-28.4%). MAFLD was associated with higher risks of incident diabetes (risk ratio [RR] 2.08; 95% CI, 1.72-2.52), CKD (RR 1.64; 95% CI, 1.39-1.94), and CVD (hazard ratio 1.44; 95% CI, 1.15-1.81). Similar associations for NAFLD were observed. Furthermore, the MAFLD subgroups with excessive alcohol consumption (RR 2.49; 95% CI, 1.64-3.78) and HBV infection (RR 1.98; 95% CI, 1.11-3.52) were associated with higher risks of incident diabetes.

Conclusion

The change from NAFLD to MAFLD did not greatly affect the associations with diabetes, CKD, and CVD. MAFLD further identified those patients of metabolically fatty liver combined with excessive alcohol consumption and HBV infection, who had increased risks of incident diabetes compared with those of non–fatty liver.
Colonic Lactulose Fermentation Has No Impact on Glucagon-like Peptide-1 and Peptide-YY Secretion in Healthy Young Men
Authors: Christiansen Charlotte Bayer , Veedfald Simon , Hartmann Bolette , Gauguin Astrid Marie , Møller Søren , Moritz Thomas , Madsbad Sten , Holst Jens Juul
Published: September 2021

Context

The colon houses most of humans’ gut microbiota, which ferments indigestible carbohydrates. The products of fermentation have been proposed to influence the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) from the many endocrine cells in the colonic epithelium. However, little is known about the colonic contribution to fasting or postprandial plasma levels of L-cell products.

Objective

To determine the impact of colonic lactulose fermentation on gut peptide secretion and to evaluate whether colonic endocrine secretion contributes to gut hormone concentrations measurable in the fasting state.

Methods

Ten healthy young men were studied on 3 occasions after an overnight fast. On 2 study days, lactulose (20 g) was given orally and compared to water intake on a third study day. For 1 of the lactulose visits, participants underwent a full colonic evacuation. Over a 6-h study protocol, lactulose fermentation was assessed by measuring exhaled hydrogen, and gut peptide secretion, paracetamol, and short-chain fatty acid levels were measured in plasma.

Results

Colonic evacuation markedly reduced hydrogen exhalation after lactulose intake (P = 0.013). Our analysis suggests that the colon does not account for the measurable amounts of GLP-1 and PYY present in the circulation during fasting and that fermentation and peptide secretion are not acutely related.

Conclusion

Whether colonic luminal contents affect colonic L-cell secretion sufficiently to influence circulating concentrations requires further investigation. Colonic evacuation markedly reduced lactulose fermentation, but hormone releases were unchanged in the present study.
Vitamin D Supplementation Improves Fasting Insulin Levels and HDL Cholesterol in Infertile Men
Authors: Holt Rune , Petersen Jørgen Holm , Dinsdale Elsa , Knop Filip Krag , Juul Anders , Jørgensen Niels , Blomberg Jensen Martin
Published: September 2021

Context

Vitamin D has been linked with glucose and lipid metabolism. Men with impaired gonadal function have a higher risk of metabolic syndrome and mortality, and vitamin D status may be a reversible modulator.

Objective

This work aimed to determine the effect of daily vitamin D and calcium supplementation for 150 days on glucose and lipid homeostasis in infertile men.

Methods

A single-center, double-blinded, randomized clinical trial (NCT01304927) was conducted. A total of 307 infertile men were randomly assigned (1:1) to a single dose of 300 000 IU cholecalciferol followed by 1400 IU cholecalciferol + 500 mg of calcium daily (n = 151) or placebo (n = 156) for 150 days. Reported metabolic parameters including fasting plasma glucose, glycated hemoglobin A1c, fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma cholesterols, and triglycerides were secondary end points. The primary end point semen quality has previously been reported.

Results

Men receiving vitamin D supplementation improved their vitamin D status, whereas vitamin D status was aggravated in the placebo group characterized by higher serum parathyroid hormone. At the end of the trial, men receiving vitamin D supplementation had 13% lower fasting serum insulin concentrations compared with the placebo-treated group (65 vs 74 pmol/L, P = .018) and 19% lower HOMA-IR (2.2 vs 2.7, P = .025). Moreover, men in the vitamin D group had higher high-density lipoprotein (HDL) cholesterol levels (1.38 vs 1.32 mmol/L, P = .008) compared with the placebo group.

Conclusion

High-dose vitamin D supplementation has beneficial effects on glucose homeostasis and HDL cholesterol levels in infertile men.
Waist-Height Ratio and the Risk of Severe Diabetic Eye Disease in Type 1 Diabetes: A 15-Year Cohort Study
Authors: Parente Erika B , Harjutsalo Valma , Forsblom Carol , Groop Per-Henrik
Published: September 2021

Context

Obesity prevalence has increased in type 1 diabetes (T1D). However, the relationship between body composition and severe diabetic eye disease (SDED) is unknown.

Objective

To investigate the associations between body composition and SDED in adults with T1D.

Methods

From 5401 adults with T1D in the Finnish Diabetic Nephropathy Study, we assessed 3468, and 437 underwent dual-energy X-ray absorptiometry for body composition analysis. The composite outcome was SDED, defined as proliferative retinopathy, laser treatment, antivascular endothelial growth factor treatment, diabetic maculopathy, vitreous hemorrhage, and vitrectomy. Logistic regression analysis evaluated the associations between body composition and SDED. Multivariable Cox regression analysis assessed the associations between the anthropometric measures and SDED. Subgroup analysis was performed by stages of albuminuria. The relevance ranking of each variable was based on the z statistic.

Results

During a median follow-up of 14.5 (interquartile range 7.8-17.5) years, 886 SDED events occurred. Visceral/android fat ratio was associated with SDED [odds ratio (OR) 1.40, z = 3.13], as well as the percentages of visceral (OR 1.80, z = 2.45) and android fat (OR 1.28, z = 2.08) but not the total body fat percentage. Waist-height ratio (WHtR) showed the strongest association with the SDED risk [hazard ratio (HR) = 1.28, z = 3.73], followed by the waist (HR 1.01, z = 3.03), body mass index (HR 1.03, z = 2.33), and waist-hip ratio (HR 1.15, z = 2.22). The results were similar in normo- and microalbuminuria but not significant in macroalbuminuria. A WHtR ≥ 0.5 increased the SDED risk by 28% at the normo- and microalbuminuria stages.

Conclusions

WHtR, a hallmark of central obesity, is associated with SDED in individuals with T1D.