bluuebunny/crossref_metadata_2025 huggingface dataset:
Long noncoding RNA NEAT1 promotes cardiac fibrosis in heart failure through increased recruitment of EZH2 to the Smad7 promoter region
Authors: Ge Zhuowang , Yin Chengye , Li Yingze , Tian Ding , Xiang Yin , Li Qianhui , Tang Yong , Zhang Yachen
Published: January 2022

Cardiac fibrosis, a well-known major pathological process that ultimately leads to heart failure, has attracted increasing attention and focus in recent years. A large amount of research indicates that long noncoding RNAs (lncRNAs) play an important role in cardiac fibrosis, but little is known about the specific function and mechanism of the lncRNA NEAT1 in the progression of cardiac fibrosis to heart failure. In the present study, we have demonstrated that the lncRNA NEAT1 is upregulated in patients with heart failure. Similarly, the expression of Neat1 was also increased in the left ventricular tissue of transverse aortic constriction (TAC) surgery mice and cardiac fibroblasts treated with TGF-β1. Further, gain-of-function and loss-of-function experiments showed that silencing of Neat1 attenuated cardiac fibrosis, while overexpression of Neat1 with adenovirus significantly aggravated the in vitro progression of fibrosis. With regard to the underlying mechanism, our experiments showed that Neat1 recruited EZH2 to the promoter region of Smad7 through physical binding of EZH2 to the promoter region, as a result of which Smad7 expression was inhibited and the progression of cardiac fibrosis was ultimately exacerbated. We found that the introduction of shNeat1 carried by adeno-associated virus-9 significantly ameliorated cardiac fibrosis and dysfunction caused by TAC surgery in mice. Overall, our study findings demonstrate that the lncRNA Neat1 accelerates the progression of cardiac fibrosis and dysfunction by recruiting EZH2 to suppress Smad7 expression. Thus, NEAT1 may serve as a target for the treatment of cardiac fibrosis.
Clinical characteristics and outcomes of chronic nonbacterial osteomyelitis in children: a multicenter case series
Authors: Ma Le , Liu Haimei , Tang Hanyun , Zhang Zhiyong , Zou Lixia , Yu Haiguo , Sun Li , Li Xiaozhong , Tang Xuemei , Lu Meiping
Published: January 2022

Objective

The aim of this study was to evaluate demographic, clinical, laboratory, imaging, histopathology characteristics, and treatment responses of children with Chronic nonbacterial osteomyelitis (CNO).

Methods

Retrospective multi-center case series study of pediatric patients diagnosed with CNO treated at five tertiary centers in south China.

Results

Totally there were 18 patients diagnosed as CNO between 2014 and 2020. The median age of onset was 9.2 years (range 3.7–13.1) and 55.6% were female. Median delay in diagnosis was 10.9 months (range 1.0–72.0). The most frequent presenting symptoms were bone pain (100%) and fever (44.4%). Most patients had more than one lesion (median of 5, range 1–7). Most frequently affected bones were tibiofibula (88.9%) and femur (77.8%). The MRI characteristics mainly presented as bone edema and hyperintensity in bone marrow. Bone biopsy was conducted in 11 patients (61.1%) with inflammatory cells infiltration manifested as chronic osteomyelitis, and none showed bacterial infection or tumor. In treatment, non-steroid anti-inflamatory drugs (NSAIDs) is used as the first-line drug followed by steriods, methotexate (MTX), salazosulfadimidine (SASP), Bisphosphonates and TNF-α inhibitor. Two refractory cases received combination therapy with Bisphosphonates and TNF-α inhibitor, and achieved good therapeutic effect.

Conclusions

The present study described a multicenter series of CNO from south China and highlighted the clinical features, laboratory tests, imaging characteristics and treatment outcomes. Increasing awareness of this disease is important to decrease time to diagnosis, improve access to treatment, and reduce complications.
Association between occupational noise and vibration and anxiety in the South Korean working population: a cross-sectional study
Authors: Park Minah , Nari Fatima , Jeong Wonjeong , Park Eun-Cheol , Jang Sung-In
Published: January 2022

Background

Although occupational exposure to noise and vibration is common, its effect on psychological wellbeing is poorly understood. This study investigated the relationship between occupational exposure to noise and vibration and anxiety among Korean workers.

Methods

Data from the 5th Korean Working Conditions Survey, conducted in 2017, were used. Participants were classified into four groups according to their level of exposure, and anxiety was assessed using a self-report questionnaire. Logistic regression analysis was used to examine the significance of the association between exposure and anxiety.

Results

Overall, 45,241 participants were enrolled in this study. The likelihood of anxiety increased, in both males and females, when exposed to both occupational noise and vibration (males: odds ratio (OR) = 2.25, confidence interval [CI] = 1.77–2.87; females: OR = 2.17, CI = 1.79–2.61). The association between the varying degrees of noise, vibration, and combined exposure showed a dose–response relationship among males.

Conclusions

This study revealed that occupational noise and vibration exposure is associated with anxiety. These results suggest that more detailed regulations regarding occupational noise and vibration should be developed and implemented to ensure a safer environment for workers.
Sympathetic science: analogism in Brazilian ethnobiological repertoires among quilombolas of the Atlantic forest and Amazonian ribeirinhos
Authors: Prado Helbert Medeiros , Murrieta Rui Sérgio Sereni , Shepard Glenn Harvey , de Lima Souza Tamires , Schlindwein Marcelo Nivert
Published: January 2022

Background

Drawing on Phillipe Descola’s comparative analysis of ontological regimes across cultures, this article identifiesanalogismguiding ethnobiological repertories among two distinctive traditional tropical forest communities in Brazil.

Methods

We carried out participant observation, semi-structured interviews and informal dialog with 48 individuals, amongquilombolasof the Atlantic Forest in southeastern Brazil andribeirinhosof the Amazon.

Results

We documented 60 traditional practices governed by analogical principles, comprising hunting, ethnomedical practices, food taboos, and other interactions with non-human entities. We also identify and classify the analogical principles reported in the field data. Based on this classification, we address the phenomenological dimension of the ethnobiological repertoires and discuss the epistemological and ontological foundations of this form of reasoning. We also hypothesize on the role of analogism shaping ethnobiological repertories more generally in Brazil.

Conclusion

The heuristic model we apply—articulating phenomenology, epistemology and ontology—could prove valuable in ethnobiology and the emerging field of “anthropology beyond the human.”
Skin-to-skin contact and breastfeeding practices in Nigeria: a study of socioeconomic inequalities
Authors: Ekholuenetale Michael , Barrow Amadou , Arora Amit
Published: January 2022

Background

The effects of breastfeeding practices on children’s health are undoubtedly of great interest. However, inequalities in breastfeeding practices and mother and newborn skin-to-skin contact (SSC) exist in many resource-constrained settings. This study examined the regional prevalence and socioeconomic inequalities in exclusive breastfeeding (EBF), early initiation of breastfeeding and SSC in Nigeria.

Methods

Data on 2936 infants under six months were extracted from the 2018 Nigeria Demographic and Health Survey (NDHS) to determine EBF. In addition, data on 21,569 children were analysed for early initiation of breastfeeding and SSC. Concentration index and curves were used to measure socioeconomic inequalities in EBF, early initiation of breastfeeding and SSC.

Results

The prevalence of EBF, early initiation of breastfeeding and SSC were 31.8, 44.2 and 12.1% respectively. Furthermore, Ogun state had the highest prevalence of EBF (71.4%); while Bayelsa state had the highest prevalence of SSC (67.8%) and early initiation of breastfeeding (96.2%) respectively. Urban dwellers had higher prevalence of EBF, SSC and early initiation of breastfeeding across household wealth quintile and by levels of mothers’ education in contrast to their rural counterparts. We quantified inequalities in early initiation of breastfeeding, EBF, and SSC according to household wealth and maternal education. The study outcomes had greater coverage in higher household wealth, in contrast to the lower household wealth groups; early initiation of breastfeeding (concentration index = 0.103; p = 0.002), EBF (concentration index = 0.118; p < 0.001), and SSC (concentration index = 0.152; p < 0.001) respectively. Furthermore, early initiation of breastfeeding (concentration index = 0.091; p < 0.001), EBF (concentration index = 0.157; p < 0.001) and SSC (concentration index = 0.156; p < 0.001) had greater coverage among mothers with higher educational attainment.

Conclusion

Low prevalence and socioeconomic inequalities in early initiation of breastfeeding, EBF and SSC were identified. We recommend that health promotion programs targeted and co-designed with disadvantaged mothers are critical to meet global breastfeeding targets. Also, future researchers should conduct further studies especially clinical control trials and qualitative studies to unravel the possible reasons for differences in the indicators.
Effect of soluble amyloid precursor protein-alpha on adult hippocampal neurogenesis in a mouse model of Alzheimer’s disease
Authors: Ohline Shane M. , Chan Connie , Schoderboeck Lucia , Wicky Hollie E. , Tate Warren P. , Hughes Stephanie M. , Abraham Wickliffe C.
Published: January 2022

Soluble amyloid precursor protein-alpha (sAPPα) is a regulator of neuronal and memory mechanisms, while also having neurogenic and neuroprotective effects in the brain. As adult hippocampal neurogenesis is impaired in Alzheimer’s disease, we tested the hypothesis that sAPPα delivery would rescue adult hippocampal neurogenesis in an APP/PS1 mouse model of Alzheimer’s disease. An adeno-associated virus-9 (AAV9) encoding murine sAPPα was injected into the hippocampus of 8-month-old wild-type and APP/PS1 mice, and later two different thymidine analogues (XdU) were systemically injected to label adult-born cells at different time points after viral transduction. The proliferation of adult-born cells, cell survival after eight weeks, and cell differentiation into either neurons or astrocytes was studied. Proliferation was impaired in APP/PS1 mice but was restored to wild-type levels by viral expression of sAPPα. In contrast, sAPPα overexpression failed to rescue the survival of XdU+-labelled cells that was impaired in APP/PS1 mice, although it did cause a significant increase in the area density of astrocytes in the granule cell layer across both genotypes. Finally, viral expression of sAPPα reduced amyloid-beta plaque load in APP/PS1 mice in the dentate gyrus and somatosensory cortex. These data add further evidence that increased levels of sAPPα could be therapeutic for the cognitive decline in AD, in part through restoration of the proliferation of neural progenitor cells in adults.
Secretory carrier-associated membrane protein 2 (SCAMP2) regulates cell surface expression of T-type calcium channels
Authors: Cmarko Leos , Stringer Robin N. , Jurkovicova-Tarabova Bohumila , Vacik Tomas , Lacinova Lubica , Weiss Norbert
Published: January 2022

Low-voltage-activated T-type Ca2+ channels are key regulators of neuronal excitability both in the central and peripheral nervous systems. Therefore, their recruitment at the plasma membrane is critical in determining firing activity patterns of nerve cells. In this study, we report the importance of secretory carrier-associated membrane proteins (SCAMPs) in the trafficking regulation of T-type channels. We identified SCAMP2 as a novel Cav3.2-interacting protein. In addition, we show that co-expression of SCAMP2 in mammalian cells expressing recombinant Cav3.2 channels caused an almost complete drop of the whole cell T-type current, an effect partly reversed by single amino acid mutations within the conserved cytoplasmic E peptide of SCAMP2. SCAMP2-induced downregulation of T-type currents was also observed in cells expressing Cav3.1 and Cav3.3 channel isoforms. Finally, we show that SCAMP2-mediated knockdown of the T-type conductance is caused by the lack of Cav3.2 expression at the cell surface as evidenced by the concomitant loss of intramembrane charge movement without decrease of total Cav3.2 protein level. Taken together, our results indicate that SCAMP2 plays an important role in the trafficking of Cav3.2 channels at the plasma membrane.
Stress-induced antinociception to noxious heat requires α1A-adrenaline receptors of spinal inhibitory neurons in mice
Authors: Uchiyama Sawako , Yoshihara Kohei , Kawanabe Riku , Hatada Izuho , Koga Keisuke , Tsuda Makoto
Published: January 2022

It is well known that acute exposure to physical stress produces a transient antinociceptive effect (called stress-induced analgesia [SIA]). One proposed mechanism for SIA involves noradrenaline (NA) in the central nervous system. NA has been reported to activate inhibitory neurons in the spinal dorsal horn (SDH), but its in vivo role in SIA remains unknown. In this study, we found that an antinociceptive effect on noxious heat after acute exposure to restraint stress was impaired in mice with a conditional knockout of α1A-adrenaline receptors (α1A-ARs) in inhibitory neurons (Vgat-Cre;Adra1aflox/flox mice). A similar reduction was also observed in mice treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, a selective neurotoxin for NAergic neurons in the locus coeruleus (LC). Furthermore, whole-cell patch-clamp recordings using spinal cord slices revealed that NA-induced increase in the frequency of spontaneous inhibitory postsynaptic currents in the substantia gelatinosa neurons was suppressed by silodosin, an α1A-AR antagonist, and by conditional knockout of α1A-ARs in inhibitory neurons. Moreover, under unstressed conditions, the antinociceptive effects of intrathecal NA and phenylephrine on noxious heat were lost in Vgat-Cre;Adra1aflox/flox mice. Our findings suggest that activation of α1A-ARs in SDH inhibitory neurons, presumably via LC-NAergic neurons, is necessary for SIA to noxious heat.
Correction to: Class I histone deacetylases (HDAC) critically contribute to Ewing sarcoma pathogenesis
Authors: Schmidt Oxana , Nehls Nadja , Prexler Carolin , von Heyking Kristina , Groll Tanja , Pardon Katharina , Garcia Heathcliff D. , Hensel Tim , Gürgen Dennis , Henssen Anton G. , Eggert Angelika , Steiger Katja , Burdach Stefan , Richter Günther H. S.
Published: January 2022

An amendment to this paper has been published and can be accessed via the original article.
Induction of m6A methylation in adipocyte exosomal LncRNAs mediates myeloma drug resistance
Authors: Wang Zhiming , He Jin , Bach Duc-hiep , Huang Yung-hsing , Li Zongwei , Liu Huan , Lin Pei , Yang Jing
Published: January 2022

Background

Therapeutic resistance occurs in most patients with multiple myeloma (MM). One of the key mechanisms for MM drug resistance comes from the interaction between MM cells and adipocytes that inhibits drug-induced apoptosis in MM cells; MM cells reprogram adipocytes to morph into different characterizations, including exosomes, which are important for tumor-stroma cellular communication. However, the mechanism by which exosomes mediate the cellular machinery of the vicious cycle between MM cells and adipocytes remains unclear.

Methods

Adipocytes were either isolated from bone marrow aspirates of healthy donors or MM patients or derived from mesenchymal stem cells. Co-culturing normal adipocytes with MM cells was used to generate MM-associated adipocytes. Exosomes were collected from the culture medium of adipocytes. Annexin V-binding and TUNEL assays were performed to assess MM cell apoptosis. Methyltransferase activity assay and dot blotting were used to access the m6A methylation activity of methyltransferase like 7A (METTL7A). RIP, MeRIP-seq, and RNA–protein pull down for assessing the interaction between long non-cording RNAs (LncRNAs) and RNA binding proteins were performed. Adipocyte-specific enhancer of zeste homolog 2 (EZH2) knockout mice and MM-xenografted mice were used for evaluating MM therapeutic response in vivo.

Results

Exosomes collected from MM patient adipocytes protect MM cells from chemotherapy-induced apoptosis. Two LncRNAs in particular, LOC606724 and SNHG1, are significantly upregulated in MM cells after exposure to adipocyte exosomes. The raised LncRNA levels in MM cells are positively correlated to worse outcomes in patients, indicating their clinical relevancy in MM. The functional roles of adipocyte exosomal LOC606724 or SNHG1 in inhibition of MM cell apoptosis are determined by knockdown in adipocytes or overexpression in MM cells. We discovered the interactions between LncRNAs and RNA binding proteins and identified methyltransferase like 7A (METTL7A) as an RNA methyltransferase. MM cells promote LncRNA package into adipocyte exosomes through METTL7A-mediated LncRNA m6A methylation. Exposure of adipocytes to MM cells enhances METTL7A activity in m6A methylation through EZH2-mediated protein methylation.

Conclusion

This study elucidates an unexplored mechanism of how adipocyte-rich microenvironment exacerbates MM therapeutic resistance and indicates a potential strategy to improve therapeutic efficacy by blocking this vicious exosome-mediated cycle.
CRISPR guides induce gene silencing in plants in the absence of Cas
Authors: Sharma Veerendra Kumar , Marla Sandeep , Zheng Wenguang , Mishra Divya , Huang Jun , Zhang Wei , Morris Geoffrey Preston , Cook David Edward
Published: January 2022

Background

RNA-targeting CRISPR-Cas can provide potential advantages over DNA editing, such as avoiding pleiotropic effects of genome editing, providing precise spatiotemporal regulation, and expanded function including antiviral immunity.

Results

Here, we report the use of CRISPR-Cas13 in plants to reduce both viral and endogenous RNA. Unexpectedly, we observe that crRNA designed to guide Cas13 could, in the absence of the Cas13 protein, cause substantial reduction in RNA levels as well. We demonstrate Cas13-independent guide-induced gene silencing (GIGS) in three plant species, including stable transgenic Arabidopsis. Small RNA sequencing during GIGS identifies the production of small RNA that extend beyond the crRNA expressed sequence in samples expressing multi-guide crRNA. Additionally, we demonstrate that mismatches in guide sequences at position 10 and 11 abolish GIGS. Finally, we show that GIGS is elicited by guides that lack the Cas13 direct repeat and can extend to Cas9 designed crRNA of at least 28 base pairs, indicating that GIGS can be elicited through a variety of guide designs and is not dependent on Cas13 crRNA sequences or design.

Conclusions

Collectively, our results suggest that GIGS utilizes endogenous RNAi machinery despite the fact that crRNA are unlike canonical triggers of RNAi such as miRNA, hairpins, or long double-stranded RNA. Given similar evidence of Cas13-independent silencing in an insect system, it is likely GIGS is active across many eukaryotes. Our results show that GIGS offers a novel and flexible approach to RNA reduction with potential benefits over existing technologies for crop improvement and functional genomics.
Does serum progesterone level impact the ongoing pregnancy rate in frozen embryo transfer under artificial preparation with vaginal progesterone? Study protocol for a randomized controlled trial
Authors: Haiyan Lin , Gang Yang , Yu Li , Lin Li , Xiaoli Chen , Qingxue Zhang
Published: January 2022

Background

In previous retrospective studies, low serum progesterone level on the embryo transfer day is associated with lower clinical pregnancy and ongoing pregnancy rates. Whether adding progesterone in low serum progesterone patients can rescue the outcome, there is no sufficient evidence from randomized controlled studies.

Methods

This trial is a clinical randomized controlled study (high serum progesterone vs low serum progesterone 1:1, 1:1 randomization ratio of intervention vs the control group with low serum progesterone). The eligible hormone replacement therapy—frozen embryo transfer (HRT-FET) cycles, will be recruited and randomly assigned to two parallel groups when serum progesterone is < 7.24μg/l on the day of embryo transfer for D3. The intervention group will be extrally given intramuscular progesterone 40 mg per day from D3 to 8 weeks of gestation if clinical pregnancy. The primary outcome is the ongoing pregnancy (beyond 12 weeks of gestation) rate.

Discussion

The findings of this study will provide strong evidence for whether the progesterone addition from the D3 in low serum progesterone patients can improve the outcome in the HRT-FET cycle.

Trial registration

ClinicalTrials.govNCT04248309. Registered on January 28, 2020
The presence of non-criteria manifestations negatively affects the prognosis of seronegative antiphospholipid syndrome patients: a multicenter study
Authors: da Rosa Gilberto Pires , Sousa-Pinto Bernardo , Ferreira Ester , Araújo Olga , Barilaro Giuseppe , Bettencourt Paulo , Cervera Ricard , Espinosa Gerard
Published: January 2022

Background

Seronegative antiphospholipid syndrome (SN-APS) is often defined as the presence of APS criteria manifestations, negative antiphospholipid antibodies (aPL), and coexistence of APS non-criteria manifestations. Nevertheless, the impact of these non-criteria features is still unclear. On a different note, the relevance of one single aPL positive determination in patients with APS manifestations is another domain with limited evidence. We aim to compare the course of SN-APS and single-positive aPL (SP-aPL) patients with that of individuals with APS manifestations without non-criteria features/aPL positivity (controls).

Methods

Retrospective analysis of patients with thrombosis/obstetric morbidity assessed in two European hospitals between 2005 and 2020. Patients were divided into SN-APS, SP-aPL, and control groups. Clinical characteristics, comorbidities, and therapies were compared.

Results

A total of 82 patients were included in the SN-APS group, 88 in the SP-aPL group, and 185 in the control group. In Cox regression model, SN-APS displayed more thrombosis recurrence than controls (HR 3.8, 95% CI 2.2–6.5,p < 0.001) even when adjusting for the presence of hereditary thrombophilia, systemic lupus erythematosus, or contraceptive hormonal treatment. In SP-aPL, the difference in thrombosis recurrence did not reach statistical significance (p = 0.078). Indefinite anticoagulation (p < 0.001 andp = 0.008, respectively) and vitamin K antagonist (VKA) use (p < 0.001 in both cases) were more common in SN-APS/SP-aPL.

Conclusion

SN-APS displayed more thrombosis recurrence, indefinite anticoagulation, and VKA use than controls without non-criteria manifestations. The presence of such features in patients with thrombosis and negative aPL may negatively impact their clinical course.
Global, regional, and national burdens of hip osteoarthritis from 1990 to 2019: estimates from the 2019 Global Burden of Disease Study
Authors: Fu Ming , Zhou Hongming , Li Yushi , Jin Hai , Liu Xiqing
Published: January 2022

Background

Hip osteoarthritis is a common disabling condition of the hip joint and is associated with a substantial health burden. We assessed the epidemiological patterns of hip osteoarthritis from 1990 to 2019 by sex, age, and socio-demographic index (SDI).

Methods

Age-standardized rates (ASRs) were obtained for the incidence and disability-adjusted life years (DALYs) of hip osteoarthritis from 1990 to 2019 for 21 regions, encompassing a total of 204 countries and territories. The estimated annual percentage changes (EAPCs) of ASRs were calculated to evaluate the trends in the incidence and DALYs of hip osteoarthritis over these 30 years.

Results

Globally, from 1990 to 2019, the age-standardized incidence rate (ASIR) of hip osteoarthritis increased from 17.02 per 100,000 persons to 18.70 per 100,000 persons, with an upward trend in the EAPC of 0.32 (0.29–0.34), whereas the age-standardized DALY rate increased from 11.54 per 100,000 persons to 12.57 per 100,000 persons, with an EAPC of 0.29 (0.27–0.32). In 2019, the EAPCs of the ASIR and age-standardized DALY rate of hip osteoarthritis were positively associated with the SDI of hip osteoarthritis. In 1990 and 2019, the incidence of hip osteoarthritis was unimodally distributed across different age groups, with a peak incidence in the 60–64-year-old age group, whereas the DALYs increased with age.

Conclusions

The incidence and DALYs of hip osteoarthritis have been increasing globally. The EAPCs of the ASIR and age-standardized DALY rate were particularly significant in developed regions and varied across nations and regions, indicating the urgent need for governments and medical institutions to increase the awareness regarding risk factors, consequences of hip osteoarthritis.
Economic burden of multiple sclerosis: a cross-sectional study in Iran
Authors: Rezaee Mehdi , Keshavarz Khosro , Izadi Sadegh , Jafari Abdosaleh , Ravangard Ramin
Published: January 2022

Background

Multiple Sclerosis (MS) is a chronic debilitating disease that imposes a heavy socioeconomic burden on societies. This study aimed to determine the economic burden of MS on patients using the first (CinnoVex and ReciGen) and second (Fingolimod and Natalizumab) drug therapy lines.

Methods

This cost of illness study was an economic evaluation carried out as cross-sectional research in 2019 in southern Iran. A total of 259 patients were enrolled in two lines of drug therapy (178 patients in the first line and 81 ones in the second). The prevalence-based approach and the bottom-up approach were used to collect cost information and to calculate the costs from the societal perspective, respectively. The human capital approach was applied to calculate indirect costs. To collect the required data a researcher-made data collection form was utilized. The data were obtained using the information available in the patients’ medical records and insurance invoices as well as their self-reports or that of their companions.

Results

The results showed that the annual costs of MS in the first and second lines of drug therapy per patient were $ 1919 and $ 4082 purchasing power parity (PPP), respectively, and in total, $ 2721 PPP in 2019. The highest mean costs in both lines were those of direct medical costs, of which purchasing the main medicines in both lines accounted for the highest.

Conclusion

Considering the findings of this study and in order to reduce the burden of the disease, the following suggestions are presented: providing necessary facilities for the production of MS drugs in the country; proper and equitable distribution of neurologists; expanding the provision of home care services; and using the technologies related to the Internet, including WhatsApp, to follow up the MS patients’ treatment.
The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases
Authors: Chang Kun-Che , Liu Pei-Feng , Chang Chia-Hsuan , Lin Ying-Cheng , Chen Yen-Ju , Shu Chih-Wen
Published: January 2022

Oxidative stress is mainly caused by intracellular reactive oxygen species (ROS) production, which is highly associated with normal physiological homeostasis and the pathogenesis of diseases, particularly ocular diseases. Autophagy is a self-clearance pathway that removes oxidized cellular components and regulates cellular ROS levels. ROS can modulate autophagy activity through transcriptional and posttranslational mechanisms. Autophagy further triggers transcription factor activation and degrades impaired organelles and proteins to eliminate excessive ROS in cells. Thus, autophagy may play an antioxidant role in protecting ocular cells from oxidative stress. Nevertheless, excessive autophagy may cause autophagic cell death. In this review, we summarize the mechanisms of interaction between ROS and autophagy and their roles in the pathogenesis of several ocular diseases, including glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and optic nerve atrophy, which are major causes of blindness. The autophagy modulators used to treat ocular diseases are further discussed. The findings of the studies reviewed here might shed light on the development and use of autophagy modulators for the future treatment of ocular diseases.
Generalized fractal Jensen and Jensen–Mercer inequalities for harmonic convex function with applications
Authors: Butt Saad Ihsan , Agarwal Praveen , Yousaf Saba , Guirao Juan L. G.
Published: January 2022

In this paper, we present a generalized Jensen-type inequality for generalized harmonically convex function on the fractal sets, and a generalized Jensen–Mercer inequality involving local fractional integrals is obtained. Moreover, we establish some generalized Jensen–Mercer-type local fractional integral inequalities for harmonically convex function. Also, we obtain some generalized related results using these inequalities on the fractal space. Finally, we give applications of generalized means and probability density function.
Weighted variable Morrey–Herz estimates for fractional Hardy operators
Authors: Asim Muhammad , Hussain Amjad , Sarfraz Naqash
Published: January 2022

The present article discusses the boundedness criteria for the fractional Hardy operators on weighted variable exponent Morrey–Herz spaces ${M\dot{K}^{\alpha(\cdot),\lambda}_{q,p(\cdot)}(w)}$
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Scalability resilience framework using application-level fault injection for cloud-based software services
Authors: Al-Said Ahmad Amro , Andras Peter
Published: January 2022

This paper presents an investigation into the effect of faults on the scalability resilience of cloud-based software services. The study introduces an experimental framework using the Application-Level Fault Injection (ALFI) to investigate how the faults at the application level affect the scalability resilience and behaviour of cloud-based software services. Previous studies on scalability analysis of cloud-based software services provide a baseline of the scalability behaviour of such services, allowing to conduct in-depth scalability investigation of these services. Experimental analysis on the EC2 cloud using a real-world cloud-based software service is used to demonstrate the framework, considering delay latency of software faults with two varied settings and two demand scenarios. The experimental approach is explained in detail. Here we simulate delay latency injection with two different times, 800 and 1600 ms, and compare the results with the baseline data. The results show that the proposed approach allows a fair assessment of the fault scenario’s impact on the cloud software service’s scalability resilience. We explain the use of the methodology to determine the impact of injected faults on the scalability behaviour and resilience of cloud-based software services.
The prevalence and psychological relation of problem shopping: data from a large-scale sample from Turkey
Authors: Ünübol Başak , Ünsalver Barış Önen , Ünübol Hüseyin , Sayar Gökben Hızlı
Published: January 2022

Background

The purpose of the present study was to comprehensively examine the measurement aspects, the prevalence, and the psychological correlates of problem shopping among a large-scale national sample of Turkish adults.

Result

Participants (N = 24,380, 50% men, M age = 31.79 years, age range = 18–81 years) completed a questionnaire that comprised the Shopping Addiction Risk Questionnaire, the Brief Symptom Inventory, the Positive and Negative Affect Schedule, and the Experiences in Close Relationships-Revised. Results showed that 1.8% of the participants had probable shopping addiction. Being female, being younger, psychiatric distress, positive affect, negative affect, anxious attachment, and avoidant attachment were positive correlates of problem shopping.

Conclusion

The results of this large sample size study suggest that shopping addiction is not a rare condition in Turkey. Further research is needed to understand different motives that underlie the problematic shopping behavior in the young and female population in comparison to older and male populations. Preventive programs or any interventions for people with PSB needs to address regulation difficulties and development of healthy strategies to cope with psychiatric distress.
Patterns of handgun divestment among handgun owners in California
Authors: Swanson Sonja A. , Miller Matthew , Zhang Yifan , Prince Lea , Holsinger Erin E. , Templeton Zachary , Studdert David M.
Published: January 2022

Background

Little is known about voluntary divestment of firearms among US firearm owners. Here, we aim to estimate the proportion of handgun owners who divest their handguns in the years following their initial acquisition; examine the timing, duration, and dynamics of those divestments; and describe characteristics of those who divest.

Methods

We use data from the Longitudinal Study of Handgun Ownership and Transfer, a cohort of registered voters in California with detailed information on 626,756 adults who became handgun owners during the 12-year study period, 2004–2016. For the current study, persons were followed from the time of their initial handgun acquisition until divestment, loss to follow-up, death, or the end of the study period. We describe the cumulative proportion who divest overall and by personal and area-level characteristics. We also estimate the proportion who reacquired handguns among persons who divested.

Results

Overall, 4.5% (95% CI 4.5–4.6) of handgun owners divested within 5 years of their first acquisition, with divestment relatively more common among women and among younger adults. Among those who divested, 36.6% (95% CI 35.8–37.5) reacquired a handgun within 5 years.

Conclusions

Handgun divestment is rare, with the vast majority of new handgun owners retaining them for years.
Endurance running during late murine adolescence results in a stronger anterior cruciate ligament and flatter posterior tibial slopes compared to controls
Authors: Ochocki Danielle N. , Loflin Benjamin E. , Ahn Taeyong , Colglazier Kaitlyn A. , Young Andrew R. , Snider Anna A. , Bueckers Elizabeth P. , Wojtys Edward M. , Schlecht Stephen H.
Published: January 2022

Background

Anterior cruciate ligament (ACL) injury rates continue to rise among youth involved in recreational and competitive athletics, requiring a better understanding of how the knee structurally and mechanically responds to activity during musculoskeletal growth. Little is understood about how anatomical risk factors for ACL injury (e.g., small ACL size, narrow intercondylar notch, and steep posterior tibial slope) develop and respond to increased physical activity throughout growth. We hypothesized that the ACL-complex of mice engaged in moderate to strenuous physical activity (i.e., endurance running) throughout late adolescence and young adulthood would positively functionally adapt to repetitive load perturbations.

Methods

Female C57BL6/J mice (8 weeks of age) were either provided free access to a standard cage wheel with added resistance (n = 18) or normal cage activity (n = 18), for a duration of 4 weeks. Daily distance ran, weekly body and food weights, and pre- and post-study body composition measures were recorded. At study completion, muscle weights, three-dimensional knee morphology, ACL cross-sectional area, and ACL mechanical properties of runners and nonrunners were quantified. Statistical comparisons between runners and nonrunners were assessed using a two-way analysis of variance and a Tukey multiple comparisons test, with body weight included as a covariate.

Results

Runners had larger quadriceps (p = 0.02) and gastrocnemius (p = 0.05) muscles, but smaller hamstring (p = 0.05) muscles, compared to nonrunners. Though there was no significant difference in ACL size (p = 0.24), it was 13% stronger in runners (p = 0.03). Additionally, both the posterior medial and lateral tibial slopes were 1.2 to 2.2 degrees flatter than those of nonrunners (p < 0.01).

Conclusions

Positive functional adaptations of the knee joint to moderate to strenuous exercise in inbred mice offers hope that that some anatomical risk factors for ACL injury may be reduced through habitual physical activity. However, confirmation that a similar response to loading occurs in humans is needed.
Radiographic vs. MRI vs. arthroscopic assessment and grading of knee osteoarthritis - are we using appropriate imaging?
Authors: Newman Samuel , Ahmed Huzefah , Rehmatullah Nader
Published: January 2022

Purpose

Radiographs and MRI scans are commonly used imaging techniques in the assessment of knee osteoarthritis. However, it currently remains uncertain how good a representation of the actual condition of the knee joint these investigations provide. By comparing them against arthroscopic findings the aim of our study was to conclude how accurate these imaging techniques are at grading knee osteoarthritis.

Methods

This was a retrospective study looking at knee arthroscopies performed at a tertiary centre over a 5 year period. The Outerbridge grade given at arthroscopy was correlated with pre-operative radiograph and MRI scores, so as to assess the reliability of these imaging techniques at predicting the actual severity of knee osteoarthritis seen.

Results

Kellgren-Lawrence (KL) grading of radiographs was moderately correlated with Outerbridge grades from arthroscopy for the medial compartment of the knee (Spearman’s rho (SR) 0.483,p < 0.001), with a milder correlation in the lateral compartment (SR 0.218,p = 0.003). MRI reporting of knee osteoarthritis was moderately correlated with Outerbridge grades in the medial compartment (SR 0.451,p < 0.001), mildly correlated for both the lateral (SR 0.299,p < 0.001) and patellofemoral joint compartments (SR 0.142,p = 0.054). KL and MRI grading was moderately correlated for the medial compartment (SR 0.475,p < 0.001) and mildly correlated for the lateral compartment (SR 0.277,p < 0.001).

Conclusion

The ability of radiographs to represent the actual condition of knee osteoarthritis is underestimated. KL grading especially best represents the disease seen in the medial compartment of the knee joint, with a moderate correlation to Outerbridge scores given on arthroscopic assessment. We suggest that whilst MRI is a useful tool in the investigation of knee symptoms, it is often unnecessarily used in patients with OA, when in fact, radiographs alone would be sufficient.

Evidence level

III
Using VIIRS nightlights to estimate the impact of the 2015 Nepal earthquakes
Authors: Tveit Thomas , Skoufias Emmanuel , Strobl Eric
Published: January 2022

We use Visible Infrared Imaging Radiometer Suite (VIIRS) nightlight data to model the impact of the 2015 Nepal earthquakes. More specifically, the data—showing nightlight emissions—are used to examine the extent to which there is a difference in nightlight intensity between cells damaged in the earthquake versus undamaged cells based on (1) mean comparisons; and (2) fixed effect regression models akin to the double difference method. The analysis is carried out for the entire country as well as smaller regions in and around the Central area and Kathmandu, which were the hardest hit areas. Overall, the regressions find a significant and negative effect from the initial shock, followed by a positive net effect from aid and relief efforts, which is consistent with what one would expect to find. However, the mean analysis results are inconclusive and there is substantial noise in the nightlight measurements due to how the values are produced and persistent cloud cover over Nepal.
A physiotherapy-led transition to home intervention for older adults following emergency department discharge: protocol for a pilot feasibility randomised controlled trial
Authors: Conneely Mairéad , Leahy Aoife , O’Connor Margaret , Barry Louise , Corey Gillian , Griffin Anne , O’Shaughnessy Íde , O’Carroll Ida , Leahy Siobhán , Trépel Dominic , Ryan Damian , Robinson Katie , Galvin Rose
Published: January 2022

Background

Older adults frequently attend the emergency department (ED) and experience high rates of adverse outcomes following ED presentation including functional decline, ED re-presentation and unplanned hospital admission. The development of effective interventions to prevent such outcomes is a key priority for research and service provision. This paper reports a protocol designed to evaluate the feasibility of conducting a three arm randomised controlled trial (RCT) within the ED setting and in the patient’s home. The interventions are comprehensive geriatric assessment (CGA), ED PLUS and usual care.

Methods

The ED PLUS pilot trial is designed as a feasibility RCT conducted in the ED and Acute Medical Assessment Unit of a university teaching hospital in the mid-west region of Ireland. We aim to recruit 30 patients, aged 65 years and over presenting to the ED with undifferentiated medical complaints and discharged within 72 h of index visit.

Patients will be randomised by a computer in a ratio of 1:1:1 to deliver usual care, CGA or ED PLUS during a 6-month study period. A randomised algorithm is used to perform randomization. CGA will include a medical assessment, medication review, nursing assessment, falls assessment, assessment of mobility and stairs, transfers, personal care, activities of daily living (ADLs), social supports and baseline cognition. ED PLUS, a physiotherapist led, multidisciplinary intervention, aims to bridge the transition of care between the index visit to the ED and the community by initiating a CGA intervention in the ED and implementing a 6-week follow-up self-management programme in the patient’s own home following discharge from the ED. The outcomes will be parameters of the feasibility of the intervention and trial methods and will be assessed quantitatively and qualitatively.

Discussion

Rising ED visits and an ageing population with chronic health issues render ED interventions to reduce adverse outcomes in older adults a research priority. This feasibility RCT will generate data and experience to inform the conduct and delivery of a definite RCT.

Trial registration

The trial was registered in Clinical Trials Protocols and Results System as of 21st July 2021, with registration number NCT049836020.
Metagenomic and metatranscriptomic analyses reveal minor-yet-crucial roles of gut microbiome in deep-sea hydrothermal vent snail
Authors: Yang Yi , Sun Jin , Chen Chong , Zhou Yadong , Van Dover Cindy Lee , Wang Chunsheng , Qiu Jian-Wen , Qian Pei-Yuan
Published: January 2022

Background

Marine animals often exhibit complex symbiotic relationship with gut microbes to attain better use of the available resources. Many animals endemic to deep-sea chemosynthetic ecosystems host chemoautotrophic bacteria endocellularly, and they are thought to rely entirely on these symbionts for energy and nutrition. Numerous investigations have been conducted on the interdependence between these animal hosts and their chemoautotrophic symbionts. The provannid snail Alviniconcha marisindica from the Indian Ocean hydrothermal vent fields hosts a Campylobacterial endosymbiont in its gill. Unlike many other chemosymbiotic animals, the gut of A. marisindica is reduced but remains functional; yet the contribution of gut microbiomes and their interactions with the host remain poorly characterised.

Results

Metagenomic and metatranscriptomic analyses showed that the gut microbiome of A. marisindica plays key nutritional and metabolic roles. The composition and relative abundance of gut microbiota of A. marisindica were different from those of snails that do not depend on endosymbiosis. The relative abundance of microbial taxa was similar amongst three individuals of A. marisindica with significant inter-taxa correlations. These correlations suggest the potential for interactions between taxa that may influence community assembly and stability. Functional profiles of the gut microbiome revealed thousands of additional genes that assist in the use of vent-supplied inorganic compounds (autotrophic energy source), digest host-ingested organics (carbon source), and recycle the metabolic waste of the host. In addition, members of five taxonomic classes have the potential to form slime capsules to protect themselves from the host immune system, thereby contributing to homeostasis. Gut microbial ecology and its interplay with the host thus contribute to the nutritional and metabolic demands of A. marisindica.

Conclusions

The findings advance the understanding of how deep-sea chemosymbiotic animals use available resources through contributions from gut microbiota. Gut microbiota may be critical in the survival of invertebrate hosts with autotrophic endosymbionts in extreme environments.
Characterization of captive and wild 13-lined ground squirrel cecal microbiotas using Illumina-based sequencing
Authors: Chiang Edna , Deblois Courtney L. , Carey Hannah V. , Suen Garret
Published: January 2022

Background

Hibernating animals experience extreme changes in diet that make them useful systems for understanding host-microbial symbioses. However, most of our current knowledge about the hibernator gut microbiota is derived from studies using captive animals. Given that there are substantial differences between captive and wild environments, conclusions drawn from studies with captive hibernators may not reflect the gut microbiota’s role in the physiology of wild animals. To address this, we used Illumina-based sequencing of the 16S rRNA gene to compare the bacterial cecal microbiotas of captive and wild 13-lined ground squirrels (TLGS) in the summer. As the first study to use Illumina-based technology to compare the microbiotas of an obligate rodent hibernator across the year, we also reported changes in captive TLGS microbiotas in summer, winter, and spring.

Results

Wild TLGS microbiotas had greater richness and phylogenetic diversity with less variation in beta diversity when compared to captive microbiotas. Taxa identified as core operational taxonomic units (OTUs) and found to significantly contribute to differences in beta diversity were primarily in the familiesLachnospiraceaeandRuminococcaceae. Captive TLGS microbiotas shared phyla and core OTUs across the year, but active season (summer and spring) microbiotas had different alpha and beta diversities than winter season microbiotas.

Conclusions

This is the first study to compare the microbiotas of captive and wild rodent hibernators. Our findings suggest that data from captive and wild ground squirrels should be interpreted separately due to their distinct microbiotas. Additionally, as the first study to compare seasonal microbiotas of obligate rodent hibernators using Illumina-based 16S rRNA sequencing, we reported changes in captive TLGS microbiotas that are consistent with previous work. Taken together, this study provides foundational information for improving the reproducibility and experimental design of future hibernation microbiota studies.