bluuebunny/crossref_metadata_2025 huggingface dataset:
TRAF4 Maintains Deubiquitination of Caveolin-1 to Drive Glioblastoma Stemness and Temozolomide Resistance
Authors: Li Yongxu , Wang Tiepeng , Wan Quan , Wang Qing , Chen Zhenzhong , Gao Yuan , Ye Yuchen , Lin Jiusheng , Zhao Bihuan , Wang Huaile , Yang Jinming , Zhao Kai , Lu Na
Published: July 2022

Glioblastoma (GBM) is the most common type of primary adult brain tumor. Glioma stem cell (GSC) residence and temozolomide (TMZ) resistance in GBM both contribute to poor patient outcome. TRAF4 is a scaffold protein with E3 ubiquitin ligase activity that has recently been discovered to promote invasion and metastasis in several malignancies, but the effects and functions of TRAF4 in GBM remain to be determined. Here, we report that TRAF4 is preferentially overexpressed in GSCs and is required for stem-like properties as well as TMZ sensitivity in GBM cells. TRAF4 specifically interacted with the N-terminal tail of Caveolin-1 (CAV1), an important contributor to the tumorigenicity of GBM cells. TRAF4 regulated CAV1 stability by preventing ZNRF1-mediated ubiquitination and facilitating USP7-mediated deubiquitination independently of its E3 ubiquitin ligase catalytic activity. TRAF4-mediated stabilization of CAV1 activated protumorigenic AKT/ERK1/2 signaling, and disruption of this axis resulted in defects in stemness maintenance. In addition, expression of TRAF4 and CAV1 was positively correlated and predicted poor prognosis in human GBM samples. Screening of common nervous system drugs identified risperidone interaction with TRAF4, and risperidone treatment resulted in the dissociation of TRAF4 and CAV1. Importantly, pharmacologic inhibition of TRAF4 with risperidone potently inhibited self-renewal, abrogated tumorigenicity, and reversed TMZ resistance in GBM. Overall, TRAF4-mediated stabilization of CAV1 promotes stemness and TMZ resistance in GBM, providing a therapeutic strategy that could improve patient outcomes.

Significance:

The identification of a TRAF4/Caveolin-1 axis that plays a crucial role in malignant progression of glioblastoma provides new insights into the function of TRAF4 in ubiquitin signaling and suggests TRAF4 as a potential therapeutic target.
GLS2 Is a Tumor Suppressor and a Regulator of Ferroptosis in Hepatocellular Carcinoma
Authors: Suzuki Sawako , Venkatesh Divya , Kanda Hiroaki , Nakayama Akitoshi , Hosokawa Hiroyuki , Lee Eunyoung , Miki Takashi , Stockwell Brent R. , Yokote Koutaro , Tanaka Tomoaki , Prives Carol
Published: July 2022

Glutamine synthase 2 (GLS2) is a key regulator of glutaminolysis and has been previously implicated in activities consistent with tumor suppression. Here we generated Gls2 knockout (KO) mice that develop late-occurring B-cell lymphomas and hepatocellular carcinomas (HCC). Further, Gls2 KO mice subjected to the hepatocarcinogenic Stelic Animal Model (STAM) protocol produce larger HCC tumors than seen in wild-type (WT) mice. GLS2 has been shown to promote ferroptosis, a form of cell death characterized by iron-dependent accumulation of lipid peroxides. In line with this, GLS2 deficiency, either in cells derived from Gls2 KO mice or in human cancer cells depleted of GLS2, conferred significant resistance to ferroptosis. Mechanistically, GLS2, but not GLS1, increased lipid reactive oxygen species (ROS) production by facilitating the conversion of glutamate to α-ketoglutarate (αKG), thereby promoting ferroptosis. Ectopic expression of WT GLS2 in a human hepatic adenocarcinoma xenograft model significantly reduced tumor size; this effect was nullified by either expressing a catalytically inactive form of GLS2 or by blocking ferroptosis. Furthermore, analysis of cancer patient datasets supported a role for GLS2-mediated regulation of ferroptosis in human tumor suppression. These data suggest that GLS2 is a bona fide tumor suppressor and that its ability to favor ferroptosis by regulating glutaminolysis contributes to its tumor suppressive function.

Significance:

This study demonstrates that the key regulator of glutaminolysis, GLS2, can limit HCC in vivo by promoting ferroptosis through αKG-dependent lipid ROS, which in turn might lay the foundation for a novel therapeutic approach.
GOT2 Silencing Promotes Reprogramming of Glutamine Metabolism and Sensitizes Hepatocellular Carcinoma to Glutaminase Inhibitors
Authors: Li Yunzheng , Li Binghua , Xu Yanchao , Qian Liyuan , Xu Tiancheng , Meng Gang , Li Huan , Wang Ye , Zhang Laizhu , Jiang Xiang , Liu Qi , Xie Yuanyuan , Cheng Chunxiao , Sun Beicheng , Yu Decai
Published: July 2022

Hepatocellular carcinoma (HCC) is one of the primary liver malignancies with a poor prognosis. Glutamic-oxaloacetic transaminase 2 (GOT2) is a highly tissue-specific gene in the liver, but the roles GOT2 plays in the progression of HCC remain unclear. Here, we report that GOT2 is downregulated in HCC tumor tissues and that low expression of GOT2 is associated with advanced progression and poor prognosis. In HCC cells, knockdown of GOT2 promoted proliferation, migration, and invasion. In mouse models of HCC, loss of GOT2 promoted tumor growth as well as hematogenous and intrahepatic metastasis. Mechanistically, silencing of GOT2 enhanced glutaminolysis, nucleotide synthesis, and glutathione synthesis by reprogramming glutamine metabolism to support the cellular antioxidant system, which activated the PI3K/AKT/mTOR pathway to contribute to HCC progression. Furthermore, HCC with low expression of GOT2 was highly dependent on glutamine metabolism and sensitive to the glutaminase inhibitor CB-839 in vitro and in vivo. Overall, GOT2 is involved in glutamine metabolic reprogramming to promote HCC progression and may serve as a therapeutic and diagnostic target for HCC.

Significance:

Altered glutamine metabolism induced by GOT2 loss supports HCC growth and metastasis but confers a targetable vulnerability to glutaminase inhibitors.
Association Between Baseline C-Reactive Protein and the Risk of Lung Cancer: A Prospective Population-Based Cohort Study
Authors: Yin Jian , Wang Gang , Wu Zheng , Lyu Zhangyan , Su Kai , Li Fang , Feng Xiaoshuang , Guo Lan-Wei , Chen Yuheng , Xie Shuanghua , Cui Hong , Li Jiang , Ren Jiansong , Shi Ju-Fang , Chen Shuohua , Wu Shouling , Dai Min , Li Ni , He Jie
Published: July 2022

C-reactive protein (CRP), a systemic marker of diagnosing chronic inflammation, has been associated with the incidence of multiple types of cancer. However, little is known about the impact of CRP on lung cancer incidence in Chinese population. A total of 97,950 participants without cancer at baseline (2006–2007) of the Kailuan Cohort Study were followed up. The concentration of plasma high-sensitivity CRP (hsCRP) was tested for all participants at baseline interview. Multivariable Cox proportional hazards regression models were used to assess the association between levels of hsCRP and incident lung cancer. During 8.7-year follow-up, 890 incident lung cancer cases occurred and were divided into three groups according to the level of hsCRP. The risk of incident lung cancer was significantly increased with elevated levels of hsCRP [HRMedium/Low, 1.21; 95% confidence interval (CI), 1.03–1.42; HRHigh/Low, 1.42, 95% CI, 1.20–1.68; Ptrend < 0.001], compared with the low group after adjusting confounders. Moreover, after stratifying by BMI, the significantly positive associations between the hsCRP level and the risk of lung cancer were found among those with BMI < 24 (HRHigh/Low, 1.51; 95% CI, 1.18–1.94; Ptrend = 0.001) and BMI = 24–28 (HRHigh/Low, 1.47; 95% CI, 1.13–1.92; Ptrend = 0.003), but not among those with BMI ≥ 28 (HRHigh/Low, 1.01; 95% CI, 0.64–1.57; Ptrend = 0.991). There was an antagonistic interaction between hsCRP levels and BMI that contributed to development of lung cancer (Pinteraction = 0.049). In conclusion, these findings indicate a dose-dependent relationship between hsCRP and lung cancer risk among Chinese population, especially in nonobese participants, suggesting that CRP could serve as a potential biomarker for prediction of lung cancer risk and identification of high-risk population.

Prevention Relevance:

In this prospective population-based cohort study, we found an association between higher plasma hsCRP and an increased risk of developing lung cancer, with stronger associations observed among nonobese participants.
CAR T-cell Therapy Meets Clonal Hematopoiesis
Authors: Uslu Ugur , June Carl H.
Published: July 2022

Clonal hematopoiesis of indeterminate potential (CHIP) is common in patients with hematologic malignancies. Recent publications provide evidence that CHIP may affect chimeric antigen receptor T-cell therapy efficacy and that the incidence of treatment-related toxicities such as cytokine release syndrome and immune effector-cell associated neurotoxicity syndrome may be affected.

See related article by Saini et al., p. 385 (8).
Curcumin Suppresses the Progression of Colorectal Cancer by Improving Immunogenic Cell Death Caused by Irinotecan
Authors: Zhu Cunliang , Fang Zhaobi , Peng Lei , Gao Fan , Peng Wei , Song Fengqian
Published: July 2022

Background: Irinotecan (IRI) is a common chemotherapeutic drug for colorectal cancer; however, the mechanism underlying its immunomodulatory effect remains unclear. Curcumin (CUR), an adjuvant drug with anti-inflammatory and antitumor effects, has been studied extensively, although its synergistic antitumor effect remains unclear. Methods: The effects of CUR and IRI on oxidative stress and their antitumor effects were detected by flow cytometry. Endoplasmic reticulum stress-related proteins including CHOP and BiP, and immunogenic cell death (ICD) proteins including calreticulin (CALR) and high mobility group box 1 (HMGB1), were detected by Western blotting. IFN-γ and TNF-α levels in the serum of mice were detected by ELISA. Results: IRI in combination with CUR had synergistic antitumor effects in CT-26 colon carcinoma cells. Combination treatment with IRI and CUR was more effective than IRI or CUR alone. IRI and CUR combination treatment significantly upregulated ICD-related proteins including CALR and HMGB1 and had a greater antitumor effect than IRI or CUR single treatment in vivo. CUR may synergistically improve the antitumor effect of IRI by promoting the ICD effect. Conclusion: Combination therapy with IRI and CUR may be an option for first-line chemotherapy in some patients with advanced colorectal cancer.
What Is Different about Teratoma-Associated Anti-LGI1 Encephalitis? A Long-Term Clinical and Neuroimaging Case Series
Authors: Li Cun , Cai Hong-bin , Zhao Xu , Xi Xin-cong , Zhou Qing , Luo Hui-ya , Tang Zhou-ping , Kang Hui-cong , Kirsch Heidi E.
Published: July 2022

Introduction: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is clinically heterogeneous, especially at presentation, and though it is sometimes found in association with tumor, this is by no means the rule. Methods: Clinical data for 10 patients with anti-LGI1 encephalitis were collected including one case with teratoma and nine cases without and compared for clinical characteristics. Microscopic pathological examination and immunohistochemical assay of the LGI1 antibody were performed on teratoma tissue obtained by laparoscopic oophorocystectomy. Results: In our teratoma-associated anti-LGI1 encephalitis case, teratoma pathology was characterized by mostly thyroid tissue and immunohistochemical assay confirmed positive nuclear staining of LGI1 in some tumor cells. The anti-LGl1 patient with teratoma was similar to the non-teratoma cases in many ways: age at onset (average 47.3 in non-teratoma cases); percent presenting with rapidly progressive dementia (67% of non-teratoma cases) and psychiatric symptoms (33%); hyponatremia (78%); normal cerebrospinal fluid results except for positive LGI1 antibody (78%); bilateral hippocampal hyperintensity on magnetic resonance imaging (44%); diffuse slow waves on electroencephalography (33%); good response to immunotherapy (67%); and mild residual cognitive deficit (22%). Her chronic anxiety and presentation with status epilepticus were the biggest differences compared with the non-teratoma cases. Conclusion: In our series, anti-LGI1 encephalitis included common clinical features in our series: rapidly progressive dementia, faciobrachial dystonic seizures, behavioral disorders, hyponatremia, hippocampal hyperintensity on magnetic resonance imaging, and residual cognitive deficit. We observed some differences (chronic anxiety and status epilepticus) in our case with teratoma, but a larger accumulation of cases is needed to improve our knowledge base.
Interstitial 2q24.2q24.3 Microdeletion: Two New Cases with Similar Clinical Features with the Exception of Profound Deafness
Authors: Tassano Elisa , Uccella Sara , Ronchetto Patrizia , Martinheira Da Silva Joana Soraia , Viaggi Silvia , Mancardi Margherita , Ramenghi Luca , Murri Alessandra , Biondi Marina , Gimelli Giorgio , Morerio Cristina , Malacarne Michela , Coviello Domenico
Published: July 2022

Interstitial 2q24.2q24.3 microdeletions are rare cytogenetic aberrations associated with heterogeneous clinical features depending on the size of the deletion. Here, we describe 2 patients with overlapping de novo 2q24.2q24.3 deletions, characterized by array-CGH. This is the smallest 2q24.2q24.3 region of overlap described in the literature encompassing only 9 genes (SLC4A10, DPP4, GCG, FAP, IFIH1, GCA, KCNH7, FIGN, GRB14). We focused our attention on SLC4A10, DPP4, and KCNH7, genes associated with neurological features. Our patients presented similar features: intellectual disability, developmental and language delay, hypotonia, joint laxity, and dysmorphic features. Only patient 2 showed profound deafness and also carried a heterozygous mutation of the GJB2 gene responsible for autosomal recessive deafness 1A (DFNB1A: OMIM 220290). Could the disruption of a gene present in the 2q24.2q24.3 deleted region be responsible for her profound hearing loss?
Phenotyping and Genotyping of HNA: Prevalence, Risk of Alloimmunization, and HNA Incompatibilities in Indians
Authors: Gogri Harita , Parihar Meghana , Kulkarni Swati , Madkaikar Manisha , Sharma Jayashree , Gorakshakar Ajit
Published: July 2022

Background: Antibodies to human neutrophil alloantigens (HNA) are involved in the pathophysiology of several clinical conditions including transfusion-related acute lung injury (TRALI), alloimmune and autoimmune neutropenia, and febrile nonhemolytic transfusion reactions leading to neutropenia. The cognate antigens are polymorphic structures expressed on several glycoproteins on the neutrophils, i.e., antigens HNA-1a, -1b, -1c, and -1d on Fc-γ-receptor IIIb; HNA-2 on CD177; HNA-3a and -3b on choline transporter-like protein 2; HNA-4a and -4b on CD11b/αM subunit of the αMβ2-integrin (CD11b/CD18, Mac-1, CR3); and HNA-5a and -5b on αL-subunit (CD11a) of the αLβ2 integrin (CD11a/CD18), leukocyte function associated molecule (LFA)-1. Currently, there is a lacuna of diagnostic methods for detection of HNA in India. This study aimed to determine the HNA frequencies in Indians, estimate the risk of alloimmunization, and prepare typed neutrophil panels, which can be used to detect HNA antibodies in neutropenia cases. Material and Methods: EDTA blood samples were collected from random 1,054 blood donors. HNA-2 was phenotyped on fresh EDTA samples using FITC labelled monoclonal anti-CD177 by flowcytometry. HNA-1 (FCGR3B) genotyping was carried out by DNA sequencing and PCR-RFLP. Antigens of HNA-3 (SLC44A2) and HNA-5 (ITGAL) were genotyped by PCR-RFLP using TaqαI and Bsp1286I restriction enzymes, respectively, while HNA-4 (ITGAM) was genotyped by PCR-SSP. Results: Allele frequencies of FCGR3B*01, FCGR3B*02, and FCGR3B*03 were found to be 0.433, 0.444, and 0.087, respectively. FCGR3B*01+*02+*03− was the most common genotype (33.78%). Ten individuals showed deficiency of FCGR3B individuals, while 23 showed hyperexpression, i.e., FCGR3B*01+*02+*03+. FCGR3B*04and *05 occurred with a frequency of 0.002 and 0.024. HNA-2 was found to be a high frequency antigen occurring in 98.8% population. Four percent individuals showed atypical expression of CD177 on their neutrophils. Allele frequencies of SLC44A2*01 and SLC44A2*02were 0.812 and 0.188, respectively, and that of ITGAM*01, ITGAM*02, ITGAL*01, and ITGAL*02 were 0.9546, 0.0454, 0.2372, and 0.7628, respectively. Conclusion: This is the first study in India to report the frequencies of HNA among blood donors. Typed neutrophil panels identified in the present study will enable us to investigate suspected cases of immune neutropenia in future.
Agreement of Cardiac Output Estimates between Electrical Cardiometry and Transthoracic Echocardiography in Very Preterm Infants
Authors: Schwarz Christoph E. , Livingstone Vicki , O’Toole John M. , Healy David B. , Panaviene Jurate , Dempsey Eugene M.
Published: July 2022

Introduction: The aim was to evaluate the agreement between cardiac output estimates obtained by electrical cardiometry (EC) and transthoracic echocardiography (TTE) in very preterm infants. Methods: This is a single-center prospective observational study in infants born<32 weeks gestational age within 48 h of birth. Continuous EC was recorded and simultaneous TTE obtained on day 1 and day 2 of life. Blinded TTE measurements were performed within a 10 s timeframe using beat-to-beat EC data. The primary outcome was %error of left ventricular (LV) output in milliliters per kilogram per minute (cardiac index (CI)) obtained by TTE compared to LV-CI from EC. Secondary outcome parameters were bias, %bias, limits of agreement and include measures of right ventricular (RV) output and LV systolic time intervals. Results: Analysis was performed for 34 infants (median (IQR) gestational age 29 + 0 (24 + 5 to 30 + 6) weeks + days, birthweight 960 (748 to 1,490) grams) including 44 pairwise LV output measurements on 24 participants (22 on day 1 and day 2). The %error was 54% for LV-CI (EC: 214 (38) mL/kg/min vs. TTE: 163 (47) mL/kg/min). The %error was 78% for RV-CI (EC: 213 (37) mL/kg/min vs. TTE: 241 (77) mL/kg/min). While only LV-CI values affected LV-CI bias, signal quality, heart rate, and RV-CI values affected RV-CI bias. Conclusion: EC is not interchangeable with TTE to estimate indices of LV or RV output in very preterm infants within the first 48 h postnatally. EC may not measure LV output distinctly in very preterm infants with intra- and extracardiac shunts.
Association of Dual Sensory Impairment with Cognitive Decline in Older Adults
Authors: Tomida Kouki , Lee Sangyoon , Bae Seongryu , Harada Kenji , Katayama Osamu , Makino Keitaro , Chiba Ippei , Morikawa Masanori , Shimada Hiroyuki
Published: July 2022

Introduction: The prevalence of hearing and visual impairment (HI and VI) and dual sensory impairment (DSI), which is a combination of both, is increasing as the population ages. These sensory impairments are expected to increase the cognitive load of information processing from hearing and vision and impair appropriate cognitive processing. Although an association between DSI and cognitive decline has been reported, a more detailed study of the effects on each cognitive domain is required. This study aimed to investigate the prevalence of self-reported sensory impairment in community-dwelling older adults and to examine the impact of DSI on the severity of mild cognitive impairment (MCI) and on each cognitive domain (memory, attention, executive function, and processing speed). Methods: The participants were recruited from a sub-cohort of the National Center for Geriatric Gerontology-Study on Geriatric Syndromes (NCGG-SGS) conducted by the National Center for Geriatrics and Gerontology. We included 4,471 community-dwelling older adults (age: 75.9 ± 4.3 years; females: 52.3%) who fulfilled the inclusion criteria. The HI and VI were identified using a self-report questionnaire. Cognitive and other parameters were also assessed by trained staff. Logistic regression analysis was used to evaluate the relationship between the presence of HI and VI and the severity of MCI, and functional decline in each cognitive domain. Results: DSI was identified in 11.4% of community-dwelling older adults. Regarding sensory impairment and MCI severity, the odds ratio (OR) for single-domain MCI was significantly higher in VI (OR: 1.31; 95% CI: 1.06–1.61), and the OR for multiple-domain MCI was significantly higher in DSI (OR: 1.58; 95% CI: 1.10–2.29). In relation to the four cognitive domains, ORs for impaired executive function were higher for VI and DSI (VI, OR: 1.37; 95% CI: 1.09–1.72. DSI, OR: 1.39; 95% CI: 1.06–1.81). DSI also exhibited a higher odds ratio for reduced processing speed (OR: 2.03; 95% CI: 1.42–2.91). Discussion/Conclusion: DSI is predicted to increase as the population ages and is associated with various health problems. Further, DSI has been reported to decrease quality of life, which needed to establish appropriate treatment and prevention measures.
Efficacy and Safety of a Low-Flow Extracorporeal Carbon Dioxide Removal System in Acute Respiratory Failure, a Pilot Study in China
Authors: Zhang Ruhan , Tian Chao , Cai Shuhan , Ma Jing , Li Jin , Li Zhaoyang , You Jinkun , Ding Xinbo , Peng Zhiyong
Published: July 2022

Background: Low-flow extracorporeal carbon dioxide removal (LF-ECCO2R) has the potential to play an important role in the management of adults with acute respiratory failure. However, it has never been tested in China. The study aimed at exploring the safety and efficacy on LF-ECCO2R for acute respiratory failure in a Chinese tertiary intensive care unit (ICU). Materials and Methods: We performed a retrospective case note review of patients admitted to our tertiary regional ICU and commenced on LF-ECCO2R from June 2020 to September 2021. The LF-ECCO2R device we used was ProLUNG® system (Estor S.p.A., Milan, Italy). The device employed a nonporous poly-4-methyl-1-pentene membrane lung with a surface area of 1.81 m2 and run at an extracorporeal blood flow between 100 and 450 mL/min. Demographic and physiologic data (including ventilation parameters and arterial blood gases) as well as the outcome of LF-ECCO2R treatment were recorded. Results: A total of 12 cases were included. A statistically significant reduction in respiratory rate, driving pressure, PaCO2, and blood lactate was observed. In addition, there was a statistically significant improvement in pH and PaO2/FiO2. Six out of 12 patients (50%) were discharged alive from ICU. Three complications related to LF-ECCO2R were reported, none resulting in serious adverse outcomes. Conclusion: Our clinical series indicated that LF-ECCO2R seemed to be safely applied in patients with acute respiratory failure. The efficacy of CO2 removal as well as the improved respiratory parameters was also observed. However, large-scale randomized clinical trials are needed to confirm the effects.
Care Needs Profiles and Their Association with Caregiver Strain among Community-Dwelling Older Adults with Cognitive Impairment
Authors: Sung Pildoo , Chan Angelique Wei-Ming
Published: July 2022

Introduction: This study examined distinct profiles of met and unmet care needs among community-dwelling older adults with cognitive impairment and their association with caregiver strain. Methods: Latent class analysis and multivariable regression were applied to data from 266 caregivers of older Singaporeans, aged 60 years and above, with cognitive impairment. Care needs were evaluated by caregivers using the Camberwell Assessment of Need for the Elderly. Caregiver strain was measured by the Zarit Burden Interview. Results: Four need profiles were identified: (1) no need (38% of caregivers), (2) met social and memory needs (29%), (3) no social and met memory needs (17%), and (4) unmet social and memory needs (16%). The unmet social and memory needs profile was associated with a higher level of caregiver strain, compared to the no need profile. Discussion: A person-centered approach captured heterogeneity in the care needs of community-dwelling older adults with cognitive impairment. Policymakers should develop tailored interventions based on need profiles that may help reduce caregiver strain.
Mudanças Climáticas: roteiro de estudos
Authors: Lucon Oswaldo dos Santos
Published: July 2022

O aumento nos gases de efeito estufa (GEE) que tem causado o aquecimento da temperatura média global observada atualmente e, com ela, seus efeitos no sistema climático como aumento dos eventos extremos de tempo, aumento do nível do mar, degelo das calotas polares entre outros. Dentro do aspecto geral do conhecimento do clima mencionado é que se encontra o livro Mudanças Climáticas: Roteiro de Estudos. Através de uma discussão detalhada sobre a ciência do clima e utilizando dados do último relatório do Painel Intergovernamental sobre Mudanças Climáticas (Intergovernmental Panel on Climate Change, IPCC), o AR6 (Assessment Report 6), este livro apresenta de forma clara e numa linguagem acessível a um público leigo quais os impactos que o aquecimento global tem causado no mundo e em nosso país, discutindo também os conceitos de vulnerabilidade, adaptação e mitigação, onde alguns exercícios simples de compreensão dos mesmos são apresentados. Este roteiro de estudos na temática de mudanças climáticas poderá auxiliar estudantes de vários níveis, profissionais de diversas áreas e ajudar os tomadores de decisão (governo e iniciativa privada) a compreender melhor a crise climática que passamos e, com isso, trabalhar para salvar o planeta.
Effects of Walking Exercise at a Pace With Versus Without Ischemic Leg Symptoms on Functional Performance Measures in People With Lower Extremity Peripheral Artery Disease: The LITE Randomized Clinical Trial
Authors: Hammond Michael M. , Spring Bonnie , Rejeski W. Jack , Sufit Robert , Criqui Michael H. , Tian Lu , Zhao Lihui , Xu Shujun , Kibbe Melina R. , Leeuwenburgh Christiaan , Manini Todd , Forman Daniel E. , Treat‐Jacobson Diane , Polonsky Tamar S. , Bazzano Lydia , Ferrucci Luigi , Guralnik Jack , Lloyd‐Jones Donald M. , McDermott Mary M.
Published: July 2022

Background

In people with peripheral artery disease, post hoc analyses of the LITE (Low Intensity Exercise Intervention in Peripheral Artery Disease) randomized trial were conducted to evaluate the effects of walking exercise at a pace inducing ischemic leg symptoms on walking velocity and the Short Physical Performance Battery, compared with walking exercise without ischemic leg symptoms and compared with a nonexercising control group.

Methods and Results

Participants with peripheral artery disease were randomized to: home‐based walking exercise that induced ischemic leg symptoms; home‐based walking exercise conducted without ischemic leg symptoms; or a nonexercising control group for 12 months. Outcomes were change of walking velocity over 4 m and change of the Short Physical Performance Battery (0–12, with 12=best) at 6‐ and 12‐month follow‐up. A total of 264 participants (48% women, 61% Black race) were included. Compared with walking exercise without ischemic symptoms, walking exercise that induced ischemic symptoms improved change in usual‐paced walking velocity over 4 m at 6‐month (0.056 m/s [95% CI, 0.019–0.094 m/s];
P
<0.01) and 12‐month follow‐up (0.084 m/s [95% CI, 0.049–0.120 m/s];
P
<0.01), change in fast‐paced of walking velocity over 4 m at 6‐month follow‐up (
P
=0.03), and change in the Short Physical Performance Battery at 12‐month follow‐up (0.821 [95% CI, 0.309–1.334];
P
<0.01). Compared with control, walking exercise at a pace inducing ischemic symptoms improved change in usual‐paced walking velocity over 4 m at 6‐month follow‐up (0.066 m/s [95% CI, 0.021–0.111 m/s];
P
<0.01).

Conclusions

In people with peripheral artery disease, those who walked for exercise at a comfortable pace without ischemic leg symptoms slowed their walking speed during daily life and worsened the Short Physical Performance Battery score, a potentially harmful effect, compared with people who walked for exercise at a pace inducing ischemic leg symptoms. Compared with a control group who did not exercise, home‐based walking exercise at a pace inducing ischemic leg symptoms significantly improved change of walking velocity over 4 m at 6‐month follow‐up, but this benefit did not persist at 12‐month follow‐up.

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT02538900.
A Model of Semantic Completion in Generative Episodic Memory
Authors: Fayyaz Zahra , Altamimi Aya , Zoellner Carina , Klein Nicole , Wolf Oliver T. , Cheng Sen , Wiskott Laurenz
Published: July 2022

Many studies have suggested that episodic memory is a generative process, but most computational models adopt a storage view. In this article, we present a model of the generative aspects of episodic memory. It is based on the central hypothesis that the hippocampus stores and retrieves selected aspects of an episode as a memory trace, which is necessarily incomplete. At recall, the neocortex reasonably fills in the missing parts based on general semantic information in a process we call semantic completion. The model combines two neural network architectures known from machine learning, the vector-quantized variational autoencoder (VQ-VAE) and the pixel convolutional neural network (PixelCNN). As episodes, we use images of digits and fashion items (MNIST) augmented by different backgrounds representing context. The model is able to complete missing parts of a memory trace in a semantically plausible way up to the point where it can generate plausible images from scratch, and it generalizes well to images not trained on. Compression as well as semantic completion contribute to a strong reduction in memory requirements and robustness to noise. Finally, we also model an episodic memory experiment and can reproduce that semantically congruent contexts are always recalled better than incongruent ones, high attention levels improve memory accuracy in both cases, and contexts that are not remembered correctly are more often remembered semantically congruently than completely wrong. This model contributes to a deeper understanding of the interplay between episodic memory and semantic information in the generative process of recalling the past.
Permitted Sets and Convex Coding in Nonthreshold Linear Networks
Authors: Collazos Steven , Nykamp Duane
Published: July 2022

Hebbian theory proposes that ensembles of neurons form a basis for neural processing. It is possible to gain insight into the activity patterns of these neural ensembles through a binary analysis, regarding neurons as either active or inactive. The framework of permitted and forbidden sets, introduced by Hahnloser, Seung, and Slotine (2003), is a mathematical model of such a binary analysis: groups of coactive neurons can be permitted or forbidden depending on the network's structure.

In order to widen the applicability of the framework of permitted sets, we extend the permitted set analysis from the original threshold-linear regime. Specifically, we generalize permitted sets to firing rate models in which Φ is a nonnegative continuous piecewise C1 activation function. In our framework, the focus is shifted from a neuron's firing rate to its responsiveness to inputs; if a neuron's firing rate is sufficiently sensitive to changes in its input, we say that the neuron is responsive. The algorithm for categorizing a neuron as responsive depends on thresholds that a user can select arbitrarily and that are independent of the dynamics.

Given a synaptic weight matrix W, we say that a set of neurons is permitted if it is possible to find a stimulus where those neurons, and no others, remain responsive. The main coding property we establish about PΦ(W), the collection of all permitted sets of the network, is that PΦ(W) is a convex code when W is almost rank one. This means that PΦ(W) in the low-rank regime can be realized as a neural code resulting from the pattern of overlaps of receptive fields that are convex.
Periodisation and the futūḥ: Making Sense of Muḥammad’s Leadership of the Conquests in Non-Muslim Sources
Authors: Shaddel Mehdy
Published: July 2022

The past few decades have witnessed a proliferation of theories on the origins of Islam which have called into question long-held scholarly axioms. One such axiom is the traditional date of 632 CE for the death of the prophet Muḥammad, which some scholars have now sought to redate to after the beginning of the Muslim conquests on the basis of the evidence of non-Muslim sources. The present contribution aims to demonstrate that the prima facie disharmony between these sources and Muslim accounts of Muḥammad’s life and the conquests is a product of the reading imposed on both sets of data, which primarily has to do with the fact that, more often than not, modern scholarship unsuspectingly operates within the rigid framework of the classical periodisation of early Islamic history. Therefore, a revision of either the traditional date of Muḥammad’s death or the starting date of the conquests based on this evidence is uncalled for.
Restoring the King’s Creditworthiness in Troubled Times: The Mission of a Polish Prince in Genoa (1776–1777)
Authors: Zanini Andrea
Published: July 2022

The rumors that accompanied the arrival of Polish nobleman Prince Antoni Sułkowski in Genoa in 1776 offer an opportunity to examine, from a new perspective, the overall complexity behind the challenges a monarch faces when attempting to inspire and regain the faith of foreign investors after a liquidity crisis. Managing creditworthiness became crucial for the Polish king during a period characterized by increasing geopolitical tensions in which the appetites of powerful neighboring states undermined the survival of the Polish-Lithuanian Commonwealth. However, despite several economic and financial reforms implemented during those years, it was the growing uncertainty that made it difficult for both the king and the state to negotiate new loans, thus triggering a vicious cycle that contributed to the further weakening of Poland and led to its disappearance from the European political map.
Just Another Physical Wreck on the Shores of Time
Authors: Millen Lisa
Published: July 2022

This article investigates the various ways in which Pentecostals read and interpreted the narrative of the woman whom Jesus healed of an “issue of blood.” It explores the manner in which she and her experience are described and explained by Pentecostals in articles and sermons from the beginning of the movement to the present day. The article attempts to survey and analyze the different interpretations and how they have changed over time. While early pentecostal literature used the narrative as an opportunity to engage in anti-physician rhetoric and to defend the doctrine of healing in the atonement, later literature expanded the interpretation of the woman’s issue beyond physical healing to include other “issues” a person might face. Present throughout the literature is an emphasis on the woman’s faith and her personal agency to bring about the miracle. However, also present are negative interpretations of the woman and her “issue of blood.” Finally, the article looks forward to other possible interpretive strategies.
How Leibniz Read Pascal’s Geometry
Authors: Dumas Primbault Simon
Published: July 2022

Between 1675 and 1676, while in Paris, Gottfried Wilhelm Leibniz (1646–1716) got privileged access to some geometric manuscripts from late Blaise Pascal’s hand. Although said manuscripts are not extant, Leibniz’s reading notes were preserved, together with his personal papers in Hannover, under the heading “Pascaliana.” The mathematical content of these notes and the influence they had on Leibniz’s later work are quite known nowadays. At the crossroads of the history of ideas, historical epistemology, and material history, this contribution looks at Leibniz’s Pascaliana through the prism of their materiality—format, layout, organization, corrections, and additions—, and the practices it betrays—copying, commenting, excerpting. Parallel to knowing what Leibniz read in Pascal, this perspective allows us to shed light on how Leibniz read Pascal, on the very intellectual-material operations that allowed him to incorporate a foreign thought and, eventually, start developing his own.
Not Anymore in Politics: Theorising the Young Egyptian Muslim Brothers’ Political Disengagement in the aftermath of the 2013 Military Coup
Authors: Abdelgawad Doha Samir , Magued Shaimaa
Published: July 2022

This study relies on the life story narratives of 48 young members of the Egyptian Muslim Brothers in identifying the different reasons behind their political disengagement in the aftermath of the 2013 military coup. Unlike the smt scholarly writings addressing Islamists’ political disengagement within a limited scope of analysis that focuses on members leaving their groups rather than politics, this study presents a multi-layered approach that examines the interplay between youth’s personal experiences, the repressive macro political conditions, and the organizational decay in shaping young Muslim Brothers’ positions towards political activism.
Peasants’ Serfdom, Freedom and Mobility in the Cracow Province (1501–1800)
Authors: Wyżga Mateusz
Published: July 2022

The article analyses the mobility of peasants, especially in the context of their relations with their landlords. It considers the role of serfdom and demesne lordship, and the circumstances in which peasants left their villages, whether legally or illegally. It then examines measurements of geographical distances covered in such movements. In the period under review, the predominance of short-distance mobility was characteristic of the peasant population in the Polish Lands; the average scope of the geography of their everyday life was about 15 kilometres. What is important for today’s understanding of both serfdom in Polish history and peasant mobility, is the relationship between the landlord, the leaseholder and the serf. Another key circumstance is that, while limiting the serfs’ mobility by restricting their personal freedom, serfdom also generated mobility through various orders given to peasants with respect to transport services.
Moving up the Hill? Peasant Strategies in Times of Plague and Climate Change
Authors: Svensson Eva , Nilsson Stefan , Pettersson Susanne , Johansson Annie
Published: July 2022

The Late Medieval Agrarian Crisis is associated with a desertion of rural settlements. Farmsteads in agriculturally-marginal locations are presumed to have been among the first to be deserted. In recent decades, interdisciplinary research has instead shown several examples of increased agrarian activity, including cereal cultivation, in the fourteenth and fifteenth centuries in forested upland areas of boreal inland Scandinavia. Farmsteads and hamlets established in forested upland areas in the fourteenth century have also been discovered. The recent excavation of one such farmstead, Ivarsbråten, shows that both settlement and agrarian production at the site had been adapted to the new climatic conditions of the Little Ice Age, which involved colder and wetter weather. It is here suggested that micro-mobility, moving out of a hamlet to an upland position, was a climate adaptation strategy pursued by a small number of peasants.
Molecular phylogenetic analysis of spiny eels (Mastacembelidae: Mastacembelus) from the Rokel River basin and adjacent areas of Sierra Leone, West Africa
Authors: KANU UNISA CONTEH , ZHANG E. , JIANZHONG SHEN
Published: July 2022

Cytochrome b (Cytb) sequences from 23 specimens of Mastacembelus spp. from the Rokel River, Taia/Jong River basins, and Freetown Peninsula were used in this study. These sequences were used to perform a gene-based phylogenetic analysis along with closely allied congeneric species in the Upper Guinea Forest in Africa. The resulting phylogenies inferred from Cytb showed populations of M. liberiensis from the Rokel River basin clustered into an exclusive lineage being sister to the lineage formed by M. greshoffi from the Congo basin. The Freetown Peninsula population of M. liberiensis clustered with sequences previously identified as M. taiaensis from the Taia/Jong River basin, sister to sequences of M. taiaensis from the Rokel River basin. The paired lineages were sister to the lineage formed by sequences from samples of the Taia/Jong River basin. These findings lead to the following conclusions: (1) hidden species diversity of spiny eels exists in either the Rokel River or the Jong River basin; (2) a likely available name for this species from the Freetown Peninsula is M. laticauda distinct from M. liberiensis; (3) given the diversity within M. liberiensis observed in the rivers sampled in Sierra Leone, it seems likely that the remaining rivers of Liberia and Sierra Leone reported having M. liberiensis may also harbor undescribed diversity. It is difficult to elevate some available junior synonyms based solely on a phylogeny inferred from Cytochrome b. We suggest that more samples from the entire range of M. liberiensis are needed and an integrated approach is required.
Contribution to the knowledge of Chinese Gryllacrididae (Orthoptera) VIII: One new species of Metriogryllacris (Metriogryllacris) amitarum Group from Guangxi
Authors: YU LIJIANG , LIU HONG , BIAN XUN
Published: July 2022

This paper describes one new species of Metriogryllacris (Metriogryllacris) amitarum group from Guangxi Huaping National Nature Reserve. A key to the species group is provided. The examined specimen is deposited in Guangxi Normal University.
NORA3. Part II: Precipitation and Temperature Statistics in Complex Terrain Modeled with a Nonhydrostatic Model
Authors: Haakenstad Hilde , Breivik Øyvind
Published: July 2022

The 3-km Norwegian Reanalysis (NORA3) is a convection-permitting, nonhydrostatic hindcast for the North Sea, the Norwegian Sea, and the Barents Sea as well as the Scandinavian Peninsula. It has a horizontal resolution of 3 km and provides a full three-dimensional atmospheric state for the period 1995–2020 with a surface analysis and boundary conditions from ERA5, a global reanalysis. In complex terrain it is found to outperform both the host reanalysis ERA5 and also the earlier hydrostatic 10-km Norwegian Hindcast Archive (NORA10), in terms of 2-m temperature and daily precipitation. Of particular interest is the representation of extreme rainfall. It is found that the upper percentiles are much better represented than in ERA5, with very little bias up to 99.9%, suggesting that the new hindcast archive is well suited for hydrological mapping and extreme-value analysis of rainfall in complex terrain.

Significance Statement

High-resolution hindcasts that permit realistic convection allow very detailed modeling of the surface temperature, precipitation, and wind field in complex terrain. There is a need for detailed mapping of rainfall and temperature extremes (upper percentiles) to assess the impact of rapid climate change. We present an assessment of the performance of the model from Part I for near-surface temperature and precipitation, which are found to be much improved in comparison with ERA5 and with earlier NORA10. The focus is on the Norwegian mainland and the Svalbard Archipelago, because the complex terrain found in these regions is challenging to represent in weather prediction models. The improvement in precipitation statistics is particularly pronounced, with nearly unbiased results up to the 99.9th percentile.
Changes in Large-Scale Fall Extreme Precipitation in the Mid-Atlantic and Northeast United States, 1979–2019
Authors: Henny Lexi , Thorncroft Chris D. , Bosart Lance F.
Published: July 2022

Global Historical Climate Network (GHCN) data are used to characterize changes in large-scale fall extreme precipitation in the mid-Atlantic and the northeast United States. Days with the highest regional extreme precipitation total [extreme precipitation (EP) days] are sorted into weather types based on tropical cyclone (TC), atmospheric river (AR), and extreme integrated water vapor transport (IVT) influences. Increased cumulative precipitation from EP days is attributed primarily to three sources. First, over the mid-Atlantic states, Pennsylvania, and eastern New England, large increasing trends are found in precipitation occurring on EP days attributed to TC-related weather types. These increases are due to a late-1990s increase in TC frequency, which manifests primarily as increased TC remnants in the mid-Atlantic area. Second, over New York State and central and northern New England, there are increasing trends in EP day precipitation from AR-related weather types. Finally, there is evidence of increasing extreme IVT-related precipitation in the absence of ARs and TCs. However, when taking into account prior TC influences, it is found that a combination of TC-related weather types accounts for much of the increasing EP day precipitation trend. These trends are then compared to EP day synoptic changes relating to atmospheric moisture content and transport. Results indicate that fall EP days have become warmer and moister, but that this does not necessarily translate to higher IVT because wind speeds have stayed the same or slowed. This is consistent with fall climatological changes during the 1979–2019 analysis period, including higher atmospheric water content and slowed westerlies in the vicinity of the mid-Atlantic.

Significance Statement

This paper sorts days with high extreme precipitation totals in the mid-Atlantic and northeast United States fall into categories based on the presence of factors such as tropical cyclones (TCs), atmospheric rivers (ARs), and other extreme moisture transport. These days have become more frequent between 1979 and 2019, in part due to events with TC influences. However, the synoptic environment on extreme days has also changed, becoming warmer and moister. Many of the most extreme events involve combined AR and TC influences. This is important because it shows that 1) large-scale extreme precipitation has become more common and has changed synoptically and 2) interactions between tropical and non-tropical systems are a key factor for extreme events in this part of the country. Future work might investigate how changes in TC frequency, moisture transport, and jet stream patterns will affect these events in a future climate.
Possible Role of the Regional NDVI in the Expansion of the Chiefdom of Lijiang during the Ming Dynasty as Reflected by Historical Documents and Tree Rings
Authors: Liang Yaqun , Chen Youping , Chen Feng , Zhang Heli
Published: July 2022

Although many studies have linked complex social processes with climate change, few have examined the connections between changes in environmental factors, resources, or energy and the evolution of civilizations on the Tibetan Plateau. The Chiefdom of Lijiang was a powerful chiefdom located on the eastern Tibetan Plateau during the Ming Dynasty; it began expanding after the 1460s. Although many studies have analyzed the political and economic motivations responsible for this expansion, no high-resolution climate records representing this period of the Chiefdom of Lijiang were available until now. Here, we obtain a 621-yr reconstruction of the April–July normalized difference vegetation index (NDVI) values derived from moisture-sensitive tree rings from the eastern Tibetan Plateau. Our NDVI reconstruction accounts for 40.4% of the variability in instrumentally measured NDVI values and can effectively represent the historical changes in regional vegetation productivity that occurred on the eastern Tibetan Plateau. In combination with a reconstruction of summer temperatures on the eastern Tibetan Plateau, these results reveal that the regional climate was relatively warm and persistently wet during the period 1466–1630. This period was characterized by long periods of above-mean vegetation productivity on the eastern Tibetan Plateau that coincided with the expansion of the Chiefdom of Lijiang. We therefore propose that the NDVI anomaly and associated favorable political environment may have affected the expansion of the Chiefdom of Lijiang. Instrumental climate data and tree rings also reveal that the early twenty-first-century drought on the eastern Tibetan Plateau was the hottest drought recorded over the past six centuries, in accordance with projections of warming over the Tibetan Plateau. Future climate warming may lead to the occurrence of similar droughts, with potentially severe consequences for modern Asia.