bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Integrated UPR and ERAD in Oligodendrocytes Maintain Myelin Thickness in Adults by Regulating Myelin Protein Translation
Authors: Wu Shuangchan , Stone Sarrabeth , Nave Klaus-Armin , Lin Wensheng 
Published: September 2020

Myelin proteins, which are produced in the endoplasmic reticulum (ER), are essential and necessary for maintaining myelin structure. The integrated unfold protein response (UPR) and ER-associated degradation (ERAD) are the primary ER quality control mechanism. The adaptor protein Sel1L (Suppressor/Enhancer of Lin-12-like) controls the stability of the E3 ubiquitin ligase Hrd1 (hydroxymethylglutaryl reductase degradation protein 1), and is necessary for the ERAD activity of the Sel1L-Hrd1 complex. Herein, we showed that Sel1L deficiency specifically in oligodendrocytes caused ERAD impairment, the UPR activation, and attenuation of myelin protein biosynthesis; and resulted in late-onset, progressive myelin thinning in the CNS of adult mice (both male and female). The pancreatic ER kinase (PERK) branch of the UPR functions as the master regulator of protein translation in ER-stressed cells. Importantly, PERK inactivation reversed attenuation of myelin protein biosynthesis in oligodendrocytes and restored myelin thickness in the CNS of oligodendrocyte-specific Sel1L-deficient mice (both male and female). Conversely, blockage of proteolipid protein production exacerbated myelin thinning in the CNS of oligodendrocyte-specific Sel1L-deficient mice (both male and female). These findings suggest that impaired ERAD in oligodendrocytes reduces myelin thickness in the adult CNS through suppression of myelin protein translation by activating PERK.SIGNIFICANCE STATEMENTMyelin is an enormous extended plasma membrane of oligodendrocytes that wraps and insulates axons. Myelin structure, including thickness, was thought to be extraordinarily stable in adults. Myelin proteins, which are produced in the endoplasmic reticulum (ER), are essential and necessary for maintaining myelin structure. The integrated unfolded protein response (UPR) and ER-associated degradation (ERAD) are the primary mechanism that maintains ER protein homeostasis. Herein, we explored the role of the integrated UPR and ERAD in oligodendrocytes in regulating myelin protein production and maintaining myelin structure using mouse models. The results presented in this study imply that the integrated UPR and ERAD in oligodendrocytes maintain myelin thickness in adults by regulating myelin protein production.
Anxiety and the Neurobiology of Temporally Uncertain Threat Anticipation
Authors: Hur Juyoen , Smith Jason F. , DeYoung Kathryn A. , Anderson Allegra S. , Kuang Jinyi , Kim Hyung Cho , Tillman Rachael M. , Kuhn Manuel , Fox Andrew S. , Shackman Alexander J. 
Published: September 2020

When extreme, anxiety—a state of distress and arousal prototypically evoked by uncertain danger—can be debilitating. Uncertain anticipation is a shared feature of situations that elicit signs and symptoms of anxiety across psychiatric disorders, species, and assays. Despite the profound significance of anxiety for human health and wellbeing, the neurobiology of uncertain-threat anticipation remains unsettled. Leveraging a paradigm adapted from animal research and optimized for fMRI signal decomposition, we examined the neural circuits engaged during the anticipation of temporally uncertain and certain threat in 99 men and women. Results revealed that the neural systems recruited by uncertain and certain threat anticipation are anatomically colocalized in frontocortical regions, extended amygdala, and periaqueductal gray. Comparison of the threat conditions demonstrated that this circuitry can be fractionated, with frontocortical regions showing relatively stronger engagement during the anticipation of uncertain threat, and the extended amygdala showing the reverse pattern. Although there is widespread agreement that the bed nucleus of the stria terminalis and dorsal amygdala—the two major subdivisions of the extended amygdala—play a critical role in orchestrating adaptive responses to potential danger, their precise contributions to human anxiety have remained contentious. Follow-up analyses demonstrated that these regions show statistically indistinguishable responses to temporally uncertain and certain threat anticipation. These observations provide a framework for conceptualizing anxiety and fear, for understanding the functional neuroanatomy of threat anticipation in humans, and for accelerating the development of more effective intervention strategies for pathological anxiety.SIGNIFICANCE STATEMENTAnxiety—an emotion prototypically associated with the anticipation of uncertain harm—has profound significance for public health, yet the underlying neurobiology remains unclear. Leveraging a novel neuroimaging paradigm in a relatively large sample, we identify a core circuit responsive to both uncertain and certain threat anticipation, and show that this circuitry can be fractionated into subdivisions with a bias for one kind of threat or the other. The extended amygdala occupies center stage in neuropsychiatric models of anxiety, but its functional architecture has remained contentious. Here we demonstrate that its major subdivisions show statistically indistinguishable responses to temporally uncertain and certain threat. Collectively, these observations indicate the need to revise how we think about the neurobiology of anxiety and fear.
Children’s Relative Age and ADHD Medication Use: A Finnish Population-Based Study
Authors: Vuori Miika , Martikainen Jaana E. , Koski-Pirilä Anna , Sourander Andre , Puustjärvi Anita , Aronen Eeva T. , Chudal Roshan , Saastamoinen Leena K. 
Published: September 2020

OBJECTIVES:
The youngest children in a classroom are at increased risk of being medicated for attention-deficit/hyperactivity disorder (ADHD). We examined the association between children’s birth month and ADHD medication rates in Finland.

METHODS:
Using a population-based study, we analyzed ADHD medication use among children born in 2005 to 2007. Cases (n = 7054) were identified from the first purchase of medication for ADHD. Cox proportional hazard models and hazard ratios (HRs) were examined by birth month and sex. Finnish children start first grade in the year of their seventh birthday. The cutoff date is December 31.

RESULTS:
Risk of ADHD medication use increased throughout the year by birth month (ie, January through April to May through August to September through December). Among boys born in September to December, the association remained stable across cohorts (HR: 1.3; 95% confidence interval [CI]: 1.1–1.5). Among girls born in September to December, the HR in the 2005 cohort was 1.4 (95% CI: 1.1–1.8), whereas in the 2007 cohort it was 1.7 (95% CI: 1.3–2.2). In a restricted follow-up, which ended at the end of the year of the children’s eighth birthday, the HRs for boys and girls born in September to December 2007 were 1.5 (95% CI: 1.3–1.7) and 2.0 (95% CI: 1.5–2.8), respectively.

CONCLUSIONS:
Relative immaturity increases the likelihood of ADHD medication use in Finland. The association was more pronounced during the first school years. Increased awareness of this association is needed among clinicians and teachers.
Islam dan Kearifan Lokal Sunda ( Tradisi 10 Muharam Bubur Suro di Sumedang)
Authors: Putri Novi Andika 
Published: September 2020

Before Religion in Indonesia was Islam, they have embraced Hinduism and Buddhism. Afterwards, Islam came to Indonesia around 7 century. This is one of the reasons why Indonesia has acculturation of culture between cultures of Hindu-Buddha and Islam. At Indonesia, especially at Sumedang has a unique culture that interesting is researched. The culture is Bubur Suro that does every 10 Muharam. Bubur Suro had a long history from an ancestor. the chieftain said that the way to commemorate the Islamic new year and to remember the events of the Prophet Nuh and the Flood. In addition, this is enforced, with motivation to conserve ancestor tradition. This written uses method of history consists of heuristic, criticism, interpretation and historiography. In this research, it was revealed that the Sumedang community, especially Negarawangi village, the majority of followers of Islam who still maintain Sundanese ancestral traditions, so that every 10 Muharam they celebrate the celebration of Maulud Nabi and also the Bubur Suro ceremony. In conclusion, Islam and the Sundanese tradition in the Bubur Suro ceremony become a form of acculturation that is still maintained in the Rancakalong between Islam and the Sundanese tradition. Keywords: budaya, muharam, sumedang
Peran Dipa Nusantara Aidit pada Peristiwa Berdarah G30s Tahun 1965
Authors: Aulia Muhammad Ihsan , Samsudin Samsudin , Isana Widiati 
Published: September 2020

Dipa Nusantara Aidit was a figure in the Indonesian Communist Party since 1947. His role was very important in the events of the G30S in 1965, especially because of his political movements that resulted in the event. This writing aims to determine the biography of Dipa Nusantara Aidit and how the role of Dipa Nusantara Aidit in the G30S incident in 1965. The method used in this study is the historical method. The results of this study Dipa Nusantara Aidit was a communist figure in the Indonesian Communist Party, active in Menteng 31 by establishing Gerindom (Gerakan Indonesia Merdeka) then establishing PBK (Persatuan Buruh Kendaraan), establishing API (Angkatan Pemuda Indonesia), and LEKRA. He once served as CC PKI Secretary General and Deputy Chair of the MPRS. Aidit was also active in writing books, among his works were the History of the Indonesian Workers' Movement, Taking the Way of the Rakya, Towards a New Indonesia, the Birth of the PKI and Its Development, and the Peasants Extending Village Demons. Second, D.N. Aidit in 1953 deposed Alimin and became CC PKI Secretary General through the Plenary Session. Aidit launched various revolutionary offensive from January to September 1965. Aidit through the PKI launched various issues such as forming Force V, Nasakom and the Council of Generals which later became a bloody coup in the kidnapping of generals on October 1, 1965. Although in the end Aidit himself was captured and was killed in Boyolali on November 22, 1965.
Pemikiran Muhammad bin Sulaiman bin Saad Al-Kafiyaji dalam Bidang Sejarah: Studi Historiografi dan Filologi Terhadap Kitab Al-Mukhtas A-R Al-Mufid Fi Ilmi Al-Tarikh Abad ke-15 M
Authors: Nurcahya Nurcahya , Akbar Mahbub Hefdzil 
Published: September 2020

Al-Kafiyaji was a popular folk teacher of his time and he also mastered quite a number of scientific branches and wrote many works especially in the field of history namely the book of Mukhtasar al-MufId fi Ilmi al-Tarikh. The purpose of this study aims to determine the biography and thoughts of al-Kafiyaji in the field of history based on the book of Mukhtasar al-Mufid fi Ilmi al-Tarikh. The method used in this study is a qualitative method, namely by collecting data through literature and documentation. The data analysis technique is done by the heuristic, criticism, interpretation and historiography methods. Based on this study it was concluded that: first, Muhammad bin Sulaiman bin Saad bin Mas'ud al-Rumi Muhyiddin Abu Abdillah al-Kafiyaji al-Barumi al-Hanafi was born around 788H / 1386/7 AD in the Anatolian Caucasus region located in the Asian region of Asia small and died in Egypt, and took the education world from the land of Sham to Egypt and produced many many works especially in the field of history. Secondly, in the field of history or Tarikh he has written the work entitled Mukhtasar al-Mufid fi Ilmi al-Tarikh. In this book, al-Kafiyaji examines the principles of historiography, the basics and the problems of historiography and the virtues of experts and sciences. He also investigated the date, from the definition based on language, custom, and terminology, to the history of the Tarikh. This book discusses the goals and conditions that must be possessed by someone who will write history.
A Novel Predictive Model for Idiopathic Multicentric Castleman Disease: The International Castleman Disease Consortium Study
Authors: Yu Li , Shi Menghan , Cai Qingqing , Strati Paolo , Hagemeister Fredrick , Zhai Qiongli , Li Ling , Fang Xiaosheng , Li Jianyong , Sun Ruifang , Zhang Shanxiang , Yang Hanjin , Wang Zhaoming , Qian Wenbin , Iwaki Noriko , Sato Yasuharu , Zhang Lu , Li Jian , Oksenhendler Eric , Xu-Monette Zijun Y. , Young Ken H. 
Published: September 2020

Abstract

Background
Patients with multicentric Castleman disease (MCD) who are negative for human immunodeficiency virus and human herpesvirus 8 are considered to have idiopathic MCD (iMCD). The clinical presentation of iMCD varies from mild constitutional symptoms to life-threatening symptoms or death. The treatment strategy varies from “watchful waiting” to high-dose chemotherapy. This diverse clinical presentation calls for a classification stratification system that takes into account the severity of the disease.

Subjects, Materials, and Methods
We analyzed the clinical, laboratory, and pathologic abnormalities and treatment outcomes of 176 patients with iMCD (median follow-up duration 12 years) from the U.S. and China to better understand the characteristics and prognostic factors of this disease. This discovery set of iMCD results was confirmed from the validation set composed of additional 197 patients with iMCD organized from The International Castleman Disease Consortium.

Results
Using these data, we proposed and validated the iMCD international prognostic index (iMCD-IPI), which includes parameters related to patient characteristics (age &gt; 40 years), histopathologic features (plasma cell variant), and inflammatory consequences of iMCD (hepatomegaly and/or splenomegaly, hemoglobin &lt;80 g/L, and pleural effusion). These five factors stratified patients according to their performance status and extent of organ dysfunction into three broad categories: low risk, intermediate risk, and high risk. The iMCD-IPI score accurately predicted outcomes in the discovery study cohort, and the results were confirmed on the validation study cohort.

Conclusion
This study represents the largest series of studies on patients with iMCD in the field and proposed a novel risk-stratification model for iMCD-IPI that could be used to guide risk-stratified treatment strategies in patients with iMCD.

Implications for Practice
Patients with idiopathic multicentric Castleman disease (iMCD) can benefit from care based on clinical symptoms and disease severity. This study in 176 patients with iMCD constructed an iMCD-IPI score based on five clinical factors, including age &gt;40 years, plasmacytic variant subtype, hepatomegaly and/or splenomegaly, hemoglobin &lt;80 g/L, and pleural effusion, and stratified patients into three risk categories: low risk, intermediate risk, and high risk. The predictive value was validated in an independent set of 197 patients with iMCD from The International Castleman Disease Consortium. The proposed novel model is valuable for predicting clinical outcome and selecting optimal therapies using clinical parameters.
Modified ypTNM Staging Classification for Gastric Cancer after Neoadjuvant Therapy: A Multi-Institutional Study
Authors: Zhong Qing , Chen Qi-Yue , Parisi Amilcare , Ma Yu-Bin , Lin Guang-Tan , Desiderio Jacopo , Yan Su , Xie Jian-Wei , Wang Jia-Bin , Hou Jun-Fang , Lin Jian-Xian , Lu Jun , Cao Long-Long , Lin Mi , Tu Ru-Hong , Huang Ze-Ning , Lin Ju-Li , Liu Zhi-Yu , Que Si-Jin , Li Ping , Zheng Chao-Hui , Huang Chang-Ming 
Published: September 2020

Abstract

Background
The benefits of neoadjuvant therapy for patients with locally advanced gastric cancer (GC) are increasingly recognized. The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual first proposed ypTNM staging, but its accuracy is controversial. This study aims to develop a modified ypTNM staging.

Patients and Methods
Clinicopathological data of 1,791 patients who underwent curative-intent gastrectomy after neoadjuvant therapy in the Surveillance, Epidemiology, and End Results database, as the development cohort, were retrospectively analyzed. Modified ypTNM staging was established based on overall survival (OS). We compared the prognostic performance of the AJCC 8th edition ypTNM staging and the modified staging for patients after neoadjuvant therapy.

Results
In the development cohort, the 5-year OS for AJCC stages I, II, and III was 58.8%, 39.1%, and 21.6%, respectively, compared with 69.9%, 54.4%, 34.4%, 24.1%, and 13.6% for modified ypTNM stages IA, IB, II, IIIA, and IIIB. The modified staging had better discriminatory ability (C-index: 0.620 vs. 0.589, p &lt; .001), predictive homogeneity (likelihood ratio chi-square: 140.71 vs. 218.66, p &lt; .001), predictive accuracy (mean difference in Bayesian information criterion: 64.94; net reclassification index: 35.54%; integrated discrimination improvement index: 0.032; all p &lt; .001), and model stability (time-dependent receiver operating characteristics curves) over AJCC. Decision curve analysis showed that the modified staging achieved a better net benefit than AJCC. In external validation (n = 266), the modified ypTNM staging had superior prognostic predictive power (all p &lt; .05).

Conclusion
We have developed and validated a modified ypTNM staging through multicenter data that is superior to the AJCC 8th edition ypTNM staging, allowing more accurate assessment of the prognosis of patients with GC after neoadjuvant therapy.

Implications for Practice
The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual first proposed ypTNM staging, but its accuracy is controversial. Based on multi-institutional data, this study developed a modified ypTNM staging, which is superior to the AJCC 8th edition ypTNM staging, allowing more accurate assessment of the prognosis of patients with gastric cancer after neoadjuvant therapy.
68Ga-DOTATATE Positron Emission Tomography-Computed Tomography Quantification Predicts Response to Somatostatin Analog Therapy in Gastroenteropancreatic Neuroendocrine Tumors
Authors: Lee Hwan , Eads Jennifer R. , Pryma Daniel A. 
Published: September 2020

Abstract

Background
Somatostatin analogs (SSAs) are the frontline antitumor therapy in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A subset of patients demonstrate early disease progression on SSA therapy, yet the currently known predictors for treatment failure lack specificity to affect therapeutic decision. SSAs target tumor somatostatin receptors, the level of which can be quantitatively assessed with 68Ga-DOTATATE positron emission tomography-computed tomography (PET/CT). We investigated the ability of 68Ga-DOTATATE PET/CT to predict response to SSA therapy.

Materials and Methods
The records of 108 consecutive patients with well-differentiated grade 1–2 GEP-NETs on SSA monotherapy who received 68Ga-DOTATATE PET/CT scans were retrospectively reviewed to obtain baseline characteristics, 68Ga-DOTATATE maximum standardized uptake value (SUVmax), and progression-free survival (PFS) data. The optimal SUVmax cutoff for patient stratification was obtained with receiver operating characteristic curve analysis. PFS in the high versus low SUVmax groups was compared with Kaplan-Meier survival analysis. The effects of baseline characteristics and SUVmax on PFS were examined with univariate and multivariate Cox regression.

Results
68Ga-DOTATATE SUVmax predicted therapeutic failure with sensitivity and specificity of 39% and 98%, respectively. SUVmax of &lt;18.35 was associated with shorter PFS, which was reproduced in the subgroup analysis of SSA-naïve patients. Low SUVmax was the only predictor of early treatment failure (hazard ratio, 6.85) in multivariate analysis, as well as in the subgroup analysis of grade 2 GEP-NETs.

Conclusion
Low SUVmax on 68Ga-DOTATATE PET/CT independently predicts early failure on SSA monotherapy in patients with well-differentiated grade 1–2 GEP-NET. Patients with lack of expected benefit from SSA therapy can be readily identified using routine 68Ga-DOTATATE PET/CT with very high specificity.

Implications for Practice
Based on 68Ga-DOTATATE positron emission tomography-computed tomography imaging, clinicians can better inform patients on the expected benefit of somatostatin analog therapy for gastroenteropancreatic neuroendocrine tumors, especially when access to the therapy is difficult, and offer proactive discussion on alternative management options.
Capacity to Provide Geriatric Specialty Care for Older Adults in Community Oncology Practices
Authors: Williams Grant R. , Weaver Kathryn E. , Lesser Glenn J. , Dressler Emily , Winkfield Karen M. , Neuman Heather B. , Kazak Anne E. , Carlos Ruth , Gansauer Lucy J. , Kamen Charles S. , Unger Joseph M. , Mohile Supriya G. , Klepin Heidi D. 
Published: September 2020

Abstract

Background
American Society of Clinical Oncology guidelines recommend that patients ≥65 years of age starting chemotherapy undergo a geriatric assessment (GA) to inform and guide management; however, little is known about resources available in community oncology practices to implement these guidelines and to facilitate geriatric oncology research.

Materials and Methods
Oncology practices within the National Cancer Institute Community Oncology Research Program (NCORP) were electronically surveyed in 2017 regarding the availability of specialty providers, supportive services, and practice characteristics, as part of a larger survey of cancer care delivery research capacity.

Results
Of the 943 NCORP practices, 504 (54%) responded to the survey, representing 210 practice groups. The median new cancer cases per year ≥65 years of age was 457 (interquartile range 227–939). Of respondents, only 2.0% of practices had a fellowship-trained geriatric oncologist on staff. Geriatricians were available for consultation or comanagement at 37% of sites, and of those, only 13% had availability within the oncology clinic (5% of overall). Practice size of ≥1,000 new adult cancer cases (ages ≥18) per year was associated with higher odds (1.81, confidence interval 1.02–3.23) of geriatrician availability. Other multidisciplinary care professionals that could support GA were variably available onsite: social worker (84%), nurse navigator (81%), pharmacist (77%), dietician (71%), rehabilitative medicine (57%), psychologist (42%), and psychiatrist (37%).

Conclusion
Only a third of community oncology practices have access to a geriatrician within their group and only 5% of community sites have access within the oncology clinic. Use of primarily self-administered GA tools that direct referrals to available services may be an effective implementation strategy for guideline-based care.

Implications for Practice
Only a minority of community oncology practices in the U.S. have access to geriatric specialty care. Developing models of care that use patient-reported measures and/or other geriatric screening tools to assess and guide interventions in older adults, rather than geriatric consultations, are likely the most practical methods to improve the care of this vulnerable population.