bluuebunny/crossref_metadata_2025 huggingface dataset:
Myofibroblast‐Specific Msi2 Knockout Inhibits HCC Progression in a Mouse Model
Authors: Qu Chen , He Lu , Yao Nan , Li Jinying , Jiang Yuchuan , Li Binkui , Peng Shuang , Hu Kunpeng , Chen Dong , Chen Guo , Huang Wei , Cao Mingrong , Fan Jun , Yuan Yunfei , Ye Wencai , Hong Jian
Published: February 2021

BACKGROUND AND AIMS

Myofibroblasts play a pivotal role in the development and progression of HCC. Here, we aimed to explore the role and mechanism of myofibroblast Musashi RNA binding protein 2 (MSI2) in HCC progression.

APPROACH AND RESULTS

Myofibroblast infiltration and collagen deposition were detected and assessed in the tissues from 117 patients with HCC. Transgenic mice (Msi2ΔCol1a1
) with floxed Msi2 allele and collagen type I alpha 1 chain (Col1a1)–ligand inducible Cre recombinases (CreER) were constructed to generate a myofibroblast‐specific Msi2 knockout model. Mouse HCC cells were orthotopically transplanted into the Msi2ΔCol1a1
or the control mice (Msi2F/F
). We found that the deposition of collagen fibers, the main product of myofibroblasts, predicted a poor prognosis for HCC; meanwhile, we detected high MSI2 expression in the peritumoral infiltrated myofibroblasts. Conditional deletion of Msi2 in myofibroblasts significantly inhibited the growth of orthotopically implanted HCC, reduced both intrahepatic and lung metastasis, and prolonged the overall survival of tumor‐bearing mice (P = 0.002). In vitro analysis demonstrated that myofibroblasts promoted cell proliferation, invasion, and epithelial–mesenchymal transformation of HCC cells, whereas Msi2 deletion in myofibroblasts reversed these effects. Mechanically, Msi2 knockout decreased myofibroblast‐derived IL‐6 and IL‐11 secretion by inhibiting the extracellular signal–regulated kinase 1/2 pathway, and thus attenuated the cancer stem cell–promoting effect of myofibroblasts. Interestingly, we found that the simultaneous knockout of Msi2 in myofibroblasts and knockdown of Msi2 in HCC cells could not further attenuate the implanted HCC progression.

CONCLUSIONS

Myofibroblast‐specific Msi2 knockout abrogated the tumor‐promoting function of myofibroblasts and inhibited HCC progression in mouse models. Targeting myofibroblast MSI2 expression may therefore prove to be a therapeutic strategy for HCC treatment in the future.
Characterization of Acute HCV Infection and Transmission Networks in People Who Currently Inject Drugs in Catalonia: Usefulness of Dried Blood Spots
Authors: Antuori Adrián , Montoya Vincent , Piñeyro David , Sumoy Lauro , Joy Jeffrey , Krajden Mel , González‐Gómez Sara , Folch Cinta , Casabona Jordi , Matas Lurdes , Colom Joan , Saludes Verónica , Martró Elisa ,   on behalf of the HepCdetect II Study Group
Published: February 2021

Background and Aims

Accurate identification of recent HCV infections is critical for tracing the extent and mechanisms of ongoing transmission. We aimed to validate dried blood spot (DBS) samples for the assessment of Hepatitis C virus (HCV) genetic diversity and to determine epidemiological parameters including incidence, determinants of acute infection, and phylogenetic clustering in people who inject drugs (PWID).

Approach and Results

HCV nonstructural protein 5B next‐generation sequencing was performed from plasma and/or DBS in 220 viremic PWID from the HepCdetect II study. No significant differences were found in consensus sequences or Shannon entropy (SE) intrahost diversity estimate between paired plasma/DBS specimens. SE values were used to identify acute infections with 93.3% sensitivity (95% CI, 0.81–1.06) and 95.0% specificity (95% CI, 0.88–1.02) in a set of well‐defined controls. An acute HCV infection (either primary infection or reinfection) was detected in 13.5% of viremic participants and was associated with age ≤30 years (OR, 8.09), injecting less than daily (OR, 4.35), ≤5 years of injected drug use (OR, 3.43), sharing cocaine snorting straws (OR, 2.89), and being unaware of their HCV status (OR, 3.62). Annualized HCV incidence was estimated between 31 and 59/100 person‐years. On phylogenetic analysis, 46.8% of viremic cases were part of a transmission pair or cluster; age ≤30 years (OR, 6.16), acute infection (OR, 5.73), and infection with subtype 1a (OR, 4.78) were independently associated with this condition.

Conclusions

The results obtained from plasma and DBS characterize PWID with acute infection and those involved in ongoing HCV transmission and allow estimating incidence from cross‐sectional data. This information is critical for the design and assessment of targeted harm reduction programs and test‐and‐treat interventions and to facilitate monitoring of HCV elimination in this key population.
Rodent mnemonic similarity task performance requires the prefrontal cortex
Authors: Johnson Sarah A. , Zequeira Sabrina , Turner Sean M. , Maurer Andrew P. , Bizon Jennifer L. , Burke Sara N.
Published: February 2021

Mnemonic similarity task performance, in which a known target stimulus must be distinguished from similar lures, is supported by the hippocampus and perirhinal cortex. Impairments on this task are known to manifest with advancing age. Interestingly, disrupting hippocampal activity leads to mnemonic discrimination impairments when lures are novel, but not when they are familiar. This observation suggests that other brain structures support discrimination abilities as stimuli are learned. The prefrontal cortex (PFC) is critical for retrieval of remote events and executive functions, such as working memory, and is also particularly vulnerable to dysfunction in aging. Importantly, the medial PFC is reciprocally connected to the perirhinal cortex and neuron firing in this region coordinates communication between lateral entorhinal and perirhinal cortices to presumably modulate hippocampal activity. This anatomical organization and function of the medial PFC suggests that it contributes to mnemonic discrimination; however, this notion has not been empirically tested. In the current study, rats were trained on a LEGO object‐based mnemonic similarity task adapted for rodents, and surgically implanted with guide cannulae targeting prelimbic and infralimbic regions of the medial PFC. Prior to mnemonic discrimination tests, rats received PFC infusions of the GABAA agonist muscimol. Analyses of expression of the neuronal activity‐dependent immediate‐early gene Arc in medial PFC and adjacent cortical regions confirmed muscimol infusions led to neuronal inactivation in the infralimbic and prelimbic cortices. Moreover, muscimol infusions in PFC impaired mnemonic discrimination performance relative to the vehicle control across all testing blocks when lures shared 50–90% feature overlap with the target. Thus, in contrast hippocampal infusions, PFC inactivation impaired target‐lure discrimination regardless of the novelty or familiarity of the lures. These findings indicate the PFC plays a critical role in mnemonic similarity task performance, but the time course of PFC involvement is dissociable from that of the hippocampus.
Mental health: The burden of social stigma
Authors: Zweifel Peter
Published: February 2021

The burden of mental health has two facets, social and psychological. Social stigma causes individuals who suspect to be suffering from a mental condition to conceal it, importantly by seeking care from a nonspecialist provider willing to diagnose it as physical disease. In this way, social stigma adds to both the direct and indirect cost of mental health. A microeconomic model depicting an individual who searches for an accommodating provider leads to the prediction that individuals undertake more search in response to a higher degree of social stigma. However, this holds only in the absence of errors in decision‐making, typically as long as mental impairment is not too serious. While government and employers have an incentive to reduce the burden of social stigma, their efforts therefore need to focus on persons with a degree of mental impairment that still allows them to avoid errors in pursuing their own interest.
Teacher–child interaction quality and children's self‐regulation in toddler classrooms in Finland and Portugal
Authors: Salminen Jenni , Guedes Carolina , Lerkkanen Marja‐Kristiina , Pakarinen Eija , Cadima Joana
Published: February 2021

This study examines the association between teacher–child interaction quality and children's self‐regulation in Finnish and Portuguese toddler classrooms. The participants included 230 Finnish (M = 29; SD = 3 months) and 283 Portuguese (M = 30, SD = 4 months) toddlers and their teachers (n = 43 Finland; n = 29 Portugal). The children's behavioural self‐regulation (attention, working memory, and inhibition control) was individually tested, and the teachers evaluated the children's self‐regulation skills in the classroom. The quality of the teacher–child interactions (i.e., emotional and behavioural support and engaged support for learning) was evaluated using the CLASS‐Toddler observation instrument. The analyses were conducted with path models using a complex option. The results for Finland show that the engaged support for learning was positively associated with children's attention and inhibitory control, and emotional and behavioural support was positively associated with children's inhibitory control. For Portugal, engaged support for learning was positively associated with children's attention. The results aid in recognizing the characteristics of teacher support that is beneficial to the development of children's self‐regulation skills in two sociocultural contexts, hence being of relevance for teacher in‐ and pre‐service training.
Satellitization of Arab Media: Perceptions of Changes in Gender Relations
Authors: Roald Anne Sofie
Published: February 2021

This article explores how students living in East Amman in Jordan perceive a link between global television entertainment and social changes, particularly changes in gender relations. The study relies on a questionnaire distributed among university students in Amman in 2009 and 2010 with 946 Muslim respondents, and focus group discussions and individual interviews with 44 Muslim students living in East Amman in 2013. The theoretical framework for the discussion is cultivation theory, moral panic, and audience reception. The main conclusion from this study is that many students believe that watching television makes viewers see ‘reality’ in view of TV programs. Another conclusion is that students seem to tailor their use of television according to their own needs. A third conclusion is that many students experience moral panic and see global television as an attack on cultural values. Other students, however, welcome global television's transmission of what they consider new liberal ideas. The students’ experience is that television entertainment products such as Turkish and American films and series, have an actual impact on social changes linked to gender relations in the East Amman society. The impact of global TV on local society is envisioned as being either “good” or “bad”.
Five Questions About Arab Women's Activism Five Years After the ‘Arab Spring’
Authors: Khamis Sahar
Published: February 2021

The Arab world witnessed unprecedented waves of revolt in 2011, which have taken the whole world by surprise, and led to many unexpected outcomes and varying results. Five years after this wave of revolt, it becomes necessary to examine its wide array of effects, especially on certain groups who played a significant role in the midst of these uprisings, such as youth and women. This article addresses a number of important points pertaining to Arab women and their future, such as the effect of the turbulent political environment in the Arab region on Arab women's movements and their ability to organize; the impact of violations of human rights and the curbing of media freedom on Arab women's online and offline activism; the implications of the prevailing environment of fragmentation and polarization in many parts of the Arab world on Arab women's activism, both offline and online; rethinking the potentials and limitations of “cyberactivism” and “cyberfeminism” in terms of enhancing Arab women's empowerment, activism, and inclusion; as well as coming up with a more inclusive and comprehensive approach, which accounts for different categories of Arab women, when rethinking the notion of “cyberfeminism.”
Focused Bayesian prediction
Authors: Loaiza‐Maya Ruben , Martin Gael M. , Frazier David T.
Published: February 2021

We propose a new method for conducting Bayesian prediction that delivers accurate predictions without correctly specifying the unknown true data generating process. A prior is defined over a class of plausible predictive models. After observing data, we update the prior to a posterior over these models, via a criterion that captures a user‐specified measure of predictive accuracy. Under regularity, this update yields posterior concentration onto the element of the predictive class that maximizes the expectation of the accuracy measure. In a series of simulation experiments and empirical examples, we find notable gains in predictive accuracy relative to conventional likelihood‐based prediction.
Demonstration of the first‐pass metabolism in the skin of the hair dye, 4‐amino‐2‐hydroxytoluene, using the Chip2 skin–liver microphysiological model
Authors: Tao Thi Phuong , Brandmair Katrin , Gerlach Silke , Przibilla Julia , Géniès Camille , Jacques‐Jamin Carine , Schepky Andreas , Marx Uwe , Hewitt Nicola J. , Maschmeyer Ilka , Kühnl Jochen
Published: February 2021

We used TissUse's HUMIMIC Chip2 microfluidic model, incorporating reconstructed skin models and liver spheroids, to investigate the impact of consumer‐relevant application scenarios on the metabolic fate of the hair dye, 4‐amino‐2‐hydroxytoluene (AHT). After a single topical or systemic application of AHT to Chip2 models, medium was analysed for parent and metabolites over 5 days. The metabolic profile of a high dose (resulting in a circuit concentration of 100 μM based on 100% bioavailability) of AHT was the same after systemic and topical application to 96‐well EpiDerm™ models. Additional experiments indicated that metabolic capacity of EpiDerm™ models were saturated at this dose. At 2.5 μM, concentrations of AHT and several of its metabolites differed between application routes. Topical application resulted in a higher Cmax and a 327% higher area under the curve (AUC) of N‐acetyl‐AHT, indicating a first‐pass effect in the EpiDerm™ models. In accordance with in vivo observations, there was a concomitant decrease in the Cmax and AUC of AHT‐O‐sulphate after topical, compared with systemic application. A similar alteration in metabolite ratios was observed using a 24‐well full‐thickness skin model, EpiDermFT™, indicating that a first‐pass effect was also possible to detect in a more complex model. In addition, washing the EpiDermFT™ after 30 min, thus reflecting consumer use, decreased the systemic exposure to AHT and its metabolites. In conclusion, the skin–liver Chip2 model can be used to (a) recapitulate the first‐pass effect of the skin and alterations in the metabolite profile of AHT observed in vivo and (b) provide consumer‐relevant data regarding leave‐on/rinse‐off products.
Hydroxyapatite sonosensitization of ultrasound‐triggered, thermally responsive hydrogels: An on‐demand delivery system for bone repair applications
Authors: Levingstone Tanya , Ali Badriah , Kearney Cathal , Dunne Nicholas
Published: February 2021

While bones have the innate capability to physiologically regenerate, in certain cases regeneration is suboptimal, too slow, or does not occur. Biomaterials‐based growth factor delivery systems have shown potential for the treatment of challenging bone defects, however, achieving controlled growth factor release remains a challenge. The objective of this study was to develop a thermally responsive hydrogel for bone regeneration capable of ultrasound‐triggered on‐demand delivery of therapeutic agents. Furthermore, it was hypothesized that incorporation of hydroxyapatite (HA) into the hydrogel could increase sonosensitization, augmenting ultrasound sensitivity to enable controlled therapeutic release to the target tissue. Alginate thermally responsive P(Alg‐g‐NIPAAm) hydrogels were fabricated and varying quantities of HA (1, 3, 5, and 7% wt./vol.) incorporated. All hydrogels were highly injectable (maximum injection force below 6.5 N) and rheological characterization demonstrated their ability to gel at body temperature. The study demonstrated the ultrasound‐triggered release of sodium fluorescein (NaF), bovine serum albumin (BSA), and bone morphogenetic protein 2 (BMP‐2) from the hydrogels. Release rates of BSA and BMP‐2 were significantly enhanced in the HA containing hydrogels, confirming for the first time the role of HA as a son sensitizer. Together these results demonstrate the potential of these ultrasound‐triggered thermally responsive hydrogels for on‐demand delivery of therapeutic agents for bone regeneration.
Physical Activity and Psychosocial Factors Associated With Risk of Future Fractures in Middle-Aged Men and Women
Authors: Rogmark Cecilia , Fedorowski Artur , Hamrefors Viktor
Published: February 2021

Identification of risk factors for fractures is important for improving public health. We aimed to identify which factors related to physical activity and psychosocial situation were associated with incident fractures among 30,446 middle-aged women and men, followed from 1991–1996 to 2016, in a prospective population-based cohort study. The association between the baseline variables and first incident fracture was assessed by Cox regression models, and significant risk factors were summed into fracture risk scores. Any first incident fracture affecting spine, thoracic cage, arms, shoulders, hands, pelvis, hips, or legs was obtained from the National Patient Register, using the unique personal identity number of each citizen. A total of 8240 subjects (27%) had at least one fracture during the follow-up of median 20.7 years. Age, female sex, body mass index, previous fracture, reported family history of fracture >50 years (all p < .001), low leisure-time physical activity (p = .018), heavy work (p = .024), living alone (p = .002), smoking (p < .001), and no or high alcohol consumption (p = .005) were factors independently associated with incident fracture. The fracture risk score (0–9 points) was strongly associated with incident fracture (p for trend <.001). Among men without risk factors, the incidence rate was 5.3/1000 person-years compared with 23.2 in men with six or more risk factors (hazard ratio [HR] = 5.5; 95% confidence interval [CI] 3.7–8.2). Among women with no risk factors, the incidence rate was 10.7 compared with 28.4 in women with six or more risk factors (HR = 3.1; 95% CI 2.4–4.0). Even moderate levels of leisure-time physical activity in middle age are associated with lower risk of future fractures. In contrast, heavy work, living alone, smoking, and no or high alcohol consumption increase the risk of fracture. Our results emphasize the importance of these factors in public health initiatives for fracture prevention. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Investigation of oxidant/antioxidant and anti‐inflammatory effects of apigenin on apoptosis in sepsis‐induced rat lung
Authors: Cicek Mustafa , Unsal Velid , Doganer Adem , Demir Mehmet
Published: February 2021

We suppose that apigenin may inhibit the cellular process of sepsis‐induced lung injury, which is considered to be a major cause of morbidity and mortality, and may improve inflammation and oxidative stress. The aim of this study was to investigate the potential protective effect of apigenin in a rat model of polymicrobial sepsis. Eight groups consisting of a total of 64 female Wistar albino rats were used for this study. Pro‐inflammatory (TNF‐α, IL‐1‐β, IL‐6) and anti‐inflammatory (TGF‐β, IL‐10) cytokine levels were measured with the enzyme‐linked immunosorbent assay technique, oxidant/antioxidants parameters were measured using the spectrophotometric method and Bax and Caspase‐3 immunohistochemical methods. TNF‐α, TGF‐β, IL‐1β, and IL‐6 levels significantly increased in the sepsis‐induced group than in the control groups, while IL‐10 levels decreased. Lipid peroxidase (LPO), an oxidative stress marker, increased, while the antioxidant defense parameters of superoxide dismutase (SOD), catalase (CAT) activities, glutathione (GSH) levels decreased. Although Bax and Caspase‐3 immunoreactivity and H score levels significantly increased in the sepsis group, significant decreases were found in the groups treated with apigenin. In conclusion, we are of the opinion that apigenin treatment improves lung injury by inhibiting oxidative stress and inflammatory cell damage.
Adsorptive granulomonocytapheresis alters the gut bacterial microbiota in patients with active ulcerative colitis
Authors: Chen Xiuli , Lou Lian , Tang Haiying , Tan Xiaoyan , Bi Jian , Wu Hao , Li Na , Wang Yingde , Mao Jingwei
Published: February 2021

Background

Ulcerative colitis (UC) is a refractory disease with unclear etiology. Studies have shown that UC is closely associated with gut microbiota dysbiosis. Adsorptive granulomonocytapheresis (GMA) using an Adacolumn has been found to treat UC effectively, but its underlying mechanism of treatment has not been fully elucidated. In this study, we aimed to investigate the influence of GMA on the gut microbiota in patients with active UC.

Methods

We conducted a single‐center prospective analysis of patients with active UC who received GMA therapy and ultimately achieved clinical remission. Stool samples of healthy controls and patients before and after 5 or 10 sessions of GMA therapy were collected. Subsequently, high‐throughput sequencing of the 16S rRNA V3 and V4 gene region of the stool was conducted and clustering of operational taxonomic units and species annotation were performed.

Results

Gut microbial profiles in patients with UC were characterized by low bacterial diversity. After 5 or 10 sessions of GMA therapy, the gut microbiota diversity in patients with UC increased and was similar to that of healthy controls. UC was further characterized by increased abundances of Proteobacteria and Bacteroides, as well as decreased abundances of Faecalibacterium, Roseburia, Firmicutes, and Dialister; however, after GMA therapy, the abundance of Bacteroides decreased, whereas those of Faecalibacterium, Roseburia, and Firmicutes increased.

Conclusions

Active UC is associated with gut microbiota dysbiosis. GMA therapy exerts a strong regulatory effect on the gut microbiota in patients with UC.
POLR2A blocks osteoclastic bone resorption and protects against osteoporosis by interacting with CREB1
Authors: Liu Chuxiao , Han Yu , Zhao Xingyu , Li Bo , Xu Liwen , Li Dongsong , Li Guangyu
Published: February 2021

Bone‐resorbing osteoclasts significantly contribute to osteoporosis, and understanding the mechanisms of osteoclastogenesis is crucial for developing new drugs to treat diseases associated with bone loss. Here, we report that POLR2A is upregulated during osteoclastogenesis. Functional analyses showed that the inhibition of POLR2A decreased osteoclastogenesis, whereas the overexpression of POLR2A had completely opposite effects in vitro. Notably, the osteoclast‐specific deletion of POLR2A blocks bone resorption in vivo. Furthermore, POLR2A loss‐of‐function suppresses estrogen deficiency‐induced bone resorption. Mechanistically, POLR2A regulates the assembly of CREB1 on the regulatory elements of its target genes. Collectively, using genetic, pharmacological, and disease mouse models, we have identified a previously undescribed protein that interacts with CREB1 to regulate osteoclastic bone resorption.
Circadian clock gene BMAL1 controls testosterone production by regulating steroidogenesis‐related gene transcription in goat Leydig cells
Authors: Xiao Yaoyao , Zhao Lijia , Li Weidong , Wang Xiaoyu , Ma Tiantian , Yang Luda , Gao Lei , Li Cuimei , Zhang Manhui , Yang Dan , Zhang Jing , Jiang Haizhen , Zhao Hongcong , Wang Yiqun , Chao Hsu‐Wen , Wang Aihua , Jin Yaping , Chen Huatao
Published: February 2021

Testosterone is produced by Leydig cells (LCs) and undergoes diurnal changes in serum levels in rats, mice, and humans, but little is known in goats. The present study revealed that goat serum testosterone levels displayed diurnal rhythmic changes (peak time at ZT11.2). Immunohistochemical staining showed that BMAL1, a circadian clock protein, is highly expressed in goat LCs. ELISA revealed that both hCG (0–5 IU/ml) and 22R‐OH‐cholesterol (0–30 μM) addition stimulated testosterone synthesis in primary goat LCs in a dose‐dependent manner. Treating goat LCs with hCG (5 IU/ml) significantly increased intracellular cAMP levels. Additionally, real‐time quantitative polymerase chain reaction (PCR) analysis revealed that the circadian clock (BMAL1, PER1, PER2, DBP, and NR1D1) and steroidogenesis‐related genes (SF1, NUR77, StAR, HSD3B2, CYP17A1, CYP11A1, and HSD17B3) showed rhythmic expression patterns in goat LCs following dexamethasone synchronization. Several Bmal1‐Luc circadian oscillations were clearly observed in dexamethasone‐treated goat LCs transfected with the pLV6‐Bmal1‐Luc plasmid. BMAL1 knockdown significantly downregulated mRNA levels of PER2, NR1D1, DBP, StAR, HSD3B2, SF1, NUR77, and GATA4, and dramatically decreased StAR and HSD3B2 protein levels and testosterone production. In contrast, BMAL1 overexpression significantly increased the mRNA and protein expression levels of StAR and HSD17B3 and enhanced testosterone production. Reporter assays revealed that goat BMAL1, or in combination with mouse CLOCK, activated goat HSD17B3 transcription in vitro. These data indicate that BMAL1 contributes to testosterone production by regulating transcription of steroidogenesis‐related genes in goat LCs, providing a basis for further exploring the underlying mechanism by which the circadian clock regulates ruminant reproductive capability.
Generation of biohybrid implants using a multipotent human periodontal ligament cell line and bioactive core materials
Authors: Ono Taiga , Tomokiyo Atsushi , Ipposhi Keita , Yamashita Kozue , Alhasan M Anas , Miyazaki Yudai , Kunitomi Yoshihiro , Tsuchiya Akira , Ishikawa Kunio , Maeda Hidefumi
Published: February 2021

We aimed to generate periodontal ligament (PDL) tissue‐like structures from a multipotent human PDL cell line using three‐dimensional (3D) bioprinting technology and to incorporate these structures with bioactive core materials to develop a new biohybrid implant system. After 3D bioprinting, single‐cell spheroids were able to form 3D tubular structures (3DTBs). We established three types of complexes using 3DTBs and different core materials: 3DTB‐titanium core (TIC), 3DTB‐hydroxyapatite core (HAC), and 3DTB without a core material (WOC). The expressions of PDL‐, angiogenesis‐, cementum‐, and bone‐related genes were significantly increased in the three complexes compared with monolayer‐cultured cells. Abundant collagen fibers and cells positive for the above markers were confirmed in the three complexes. However, more positive cells were detected in HAC than in WOC or TIC. The present results suggest that 3D‐bioprinted structures and hydroxyapatite core materials can function similarly to the PDL and may be useful for the development of a new biohybrid implant system.
Genetic testing for pheochromocytoma and paraganglioma: SDHx carriers’ experiences
Authors: Martins Raquel Gomes , Carvalho Irene Palmares
Published: February 2021

Pheochromocytoma and paraganglioma are frequently hereditary tumors commonly associated with succinate dehydrogenase (SDHx) pathogenic variants (PV). Genetic testing is recommended to relatives of patients carrying SDHx PV. This study aims to explore the experiences associated with genetic testing for this hereditary condition. Semi‐structured interviews with 38 SDHx PV (tumor‐affected and non‐affected) carriers were transcribed and content‐analyzed. Four ways of living with this genetic alteration emerged from the interviews: ‘living as if not knowing’, ‘preventing others from going through this’, ‘feeling privileged’, and ‘still suffering’. Within each, negative, neutral, and positive reactions to the actual test result emerged initially, in addition to blame and guilt. Recognition of the importance of the genetic test and of the follow‐up occurred in all four, but views on fecundity were divided between having and not having children. Consideration for the four different meanings of carrying an SDHx PV can improve participants’ experiences and clinical practice.
Exploring how mothers of a child with a genetic disorder experience their couple relationship in a low socio‐economic setting
Authors: Haw Tabitha , Henriques Sasha
Published: February 2021

Having a child with a genetic disorder directly impacts a couple's relationship due to increased care demands. Most research on couple relationships in the context of having a child with a disability has been done in well‐resourced, developed countries. In South Africa, the black South African population has been historically disadvantaged resulting in high rates of unemployment and poverty, and disruption of the family system. The purpose of this study was to explore the impact of having a child with a genetic disorder on the couple relationship in a low socio‐economic setting. Thirteen black South African mothers of a child with a confirmed or suspected genetic disorder participated in the study. All participants were recruited while waiting to be seen for a follow‐up appointment by a medical geneticist at a Genetic Clinic in Johannesburg, South Africa between 2016 and 2019. Data were collected through semi‐structured interviews lasting between 25 and 60 min and analyzed using thematic content analysis. Findings showed that mothers of a child with a genetic disorder in this low socio‐economic setting frequently felt unsupported and carried the responsibility of childcare alone. The majority of participants wanted more tangible and emotional support from their partners and without this support they felt isolated and alone. The participants used many different coping strategies to deal with the distress of having a child with a genetic disorder but most frequently they described using 'acceptance'. Participants' partners were more often reported to use escape‐avoidance strategies such as abandonment, denying paternity, withdrawal, and partner‐blame. We suggest that mothers of a child with a genetic disorder should consult with a genetic counselor in addition to a medical geneticist to enable the provision of emotional support.
Coronary artery disease and non‐alcoholic fatty liver disease: Clinical correlation using computed tomography coronary calcium scans
Authors: Kirby Richard S , Halegoua‐DeMarzio Dina
Published: February 2021

Background and Aim

Non‐alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) have been explored using coronary angiography, which showed a link between severe NAFLD and cardiovascular disease risk. This study's aim is to determine if computed tomography (CT) coronary artery calcium (CAC) scores used to determine CAD severity in asymptomatic populations can help predict the presence of NAFLD.

Methods

This was a retrospective cross‐sectional study of positive CT CAC scores and liver imaging with either CT; ultrasound; magnetic resonance imaging of the abdomen; or CT of the chest, which included liver images. Drinking 7 or 14 drinks per week for a female or male, respectively, and chronic viral hepatitis diagnosis were the exclusion criteria. CT CAC scores, hepatic steatosis, age, gender, lipid and liver panels, weight, blood pressure, F‐4/BARD scores, and hemoglobin A1c were correlated to CAD severity and NAFLD by logistic regression.

Results

A total of 134 patients with a mean age of 62.3 years (σ = 9.1), with 65% males, body mass index 28.5 (σ = 6.0), and 8% diabetics, were recruited. CAD severity was not associated with the presence of hepatic steatosis (odds ratio 1.96 [95% confidence interval, confidence interval 0.74–5.23] P = 0.36). Adjusted for variables, a link between hepatic steatosis, CAD severity, body mass index over 30 (odds ratio 6.77 [95% confidence interval 1.40–32.66] P = 0.02), and diabetes (odds ratio 9.60 [95% confidence interval 0.56–165.5] P = 0.01) was observed.

Conclusions

In patients with CAD detected using a positive CT CAC scan, we determined that BMI over 30 and diabetes were correlated with the presence of NAFLD. There was no direct relationship between CAD presence and hepatic steatosis presence.
Missed opportunities for sexually transmitted infections testing for HIV pre‐exposure prophylaxis users: a systematic review
Authors: Ong Jason J , Fu Hongyun , Baggaley Rachel C , Wi Teodora E , Tucker Joseph D , Smith M Kumi , Rafael Sabrina , Falconer Jane , Terris‐Prestholt Fern , Mameletzis Ioannis , Mayaud Phillipe
Published: February 2021

Introduction

Given the synergistic relationship between HIV and sexually transmitted infections (STI), the integration of services has the potential to reduce the incidence of both HIV and STIs. We explored the extent to which STI testing has been offered within HIV pre‐exposure prophylaxis (PrEP) programmes worldwide.

Methods

We conducted a systematic review of PrEP programmes implementing STI testing services in nine databases. We approached PrEP implementers for additional unpublished data and implementation details. Descriptive statistics were used to present the characteristics of STI testing within PrEP programmes. Content analysis of the input from PrEP implementers was conducted to summarize the barriers to and facilitators of STI testing.

Results

Of 9,161 citations, 91 studies conducted in 32 countries were included: 69% from high‐income countries (HICs) and 64% from programmes targeting men who have sex with men (MSM) and transgender women (TGW) only. The majority of programmes (70%, 64/91) conducted STI testing before the initiation of PrEP. The most common STIs tested were gonorrhoea (86%, 78/91), chlamydia (84%, 76/91) and syphilis (84%, 76/91). The majority provided STI testing at three‐month intervals (70%, 53/76, for syphilis; 70% 53/78, for chlamydia; 68%, 53/78, for gonorrhoea). Relative to low‐ and middle‐income countries (LMICs), a higher proportion of PrEP programmes in HICs offered testing for gonorrhoea (92% vs. 71%, p < 0.05), chlamydia (92% vs. 64%, p < 0.01), syphilis (87% vs. 75%, p < 0.05), hepatitis A (18% vs. 4%, p < 0.05) and hepatitis C (43% vs. 21%, p < 0.05); offered testing for a higher number of STIs (mean 3.75 vs. 3.04, p < 0.05); and offered triple (throat, genital/urine and anorectal) anatomical site screening (54% vs. 18%, p < 0.001). Common implementation challenges included costs, access to STI diagnostics, programme logistics of integrating STI testing into PrEP delivery models and lack of capacity building for staff involved in PrEP provision.

Conclusions

Significant gaps and challenges remain in the provision of STI testing services within HIV PrEP programmes. We recommend more active integration of STI testing and management into PrEP programmes, supported by standardized practice guidelines, staff capacity building training and adequate funding. This could lead to improved sexual health and HIV outcomes in key populations.
IL-34 and CSF-1, deciphering similarities and differences at steady state and in diseases
Authors: Freuchet Antoine , Salama Apolline , Remy Séverine , Guillonneau Carole , Anegon Ignacio
Published: February 2021

Although IL-34 and CSF-1 share actions as key mediators of monocytes/macrophages survival and differentiation, they also display differences that should be identified to better define their respective roles in health and diseases. IL-34 displays low sequence homology with CSF-1 but has a similar general structure and they both bind to a common receptor CSF-1R, although binding and subsequent intracellular signaling shows differences. CSF-1R expression has been until now mainly described at a steady state in monocytes/macrophages and myeloid dendritic cells, as well as in some cancers. IL-34 has also 2 other receptors, protein-tyrosine phosphatase zeta (PTPζ) and CD138 (Syndecan-1), expressed in some epithelium, cells of the central nervous system (CNS), as well as in numerous cancers. While most, if not all, of CSF-1 actions are mediated through monocyte/macrophages, IL-34 has also other potential actions through PTPζ and CD138. Additionally, IL-34 and CSF-1 are produced by different cells in different tissues. This review describes and discusses similarities and differences between IL-34 and CSF-1 at steady state and in pathological situations and identifies possible ways to target IL-34, CSF-1, and its receptors.
Quantification of the Hemodynamic Changes of Cirrhosis with Free‐Breathing Self‐Navigated MRI
Authors: Brunsing Ryan L. , Brown Dustin , Almahoud Hashem , Kono Yuko , Loomba Rohit , Vodkin Irene , Sirlin Claude B. , Alley Marcus T. , Vasanawala Shreyas S. , Hsiao Albert
Published: February 2021

Background

Non‐invasive assessment of the hemodynamic changes of cirrhosis might help guide management of patients with liver disease but are currently limited.

Purpose

To determine whether free‐breathing 4D flow MRI can be used to quantify the hemodynamic effects of cirrhosis and introduce hydraulic circuit indexes of severity.

Study Type

Retrospective.

Population

Forty‐seven patients including 26 with cirrhosis.

Field Strength/Sequence

3 T/free‐breathing 4D flow MRI with soft gating and golden‐angle view ordering.

Assessment

Measurements of the supra‐celiac abdominal aorta, supra‐renal abdominal aorta (SRA), celiac trunk (CeT), superior mesenteric artery (SMA), splenic artery (SpA), common hepatic artery (CHA), portal vein (PV), and supra‐renal inferior vena cava (IVC) were made by two radiologists. Measures of hepatic vascular resistance (hepatic arterial relative resistance [HARR]; portal resistive index [PRI]) were proposed and calculated.

Statistical Analysis

Bland–Altman, Pearson's correlation, Tukey's multiple comparison, and Cohen's kappa. P < 0.05 was considered significant.

Results

Forty‐four of 47 studies yielded adequate image quality for flow quantification (94%). Arterial structures showed high inter‐reader concordance (range; ρ = 0.948–0.987) and the IVC (ρ = 0.972), with moderate concordance in the PV (ρ = 0.866). Conservation of mass analysis showed concordance between large vessels (SRA vs. IVC; ρ = 0.806), small vessels (celiac vs. CHA + SpA; ρ = 0.939), and across capillary beds (CeT + SMA vs. PV; ρ = 0.862). Splanchnic flow was increased in patients with portosystemic shunting (PSS) relative to control patients and patients with cirrhosis without PSS (P < 0.05, difference range 0.11–0.68 liter/m). HARR was elevated and PRI was decreased in patients with PSS (3.55 and 1.49, respectively) compared to both the control (2.11/3.18) and non‐PSS (2.11/2.35) cohorts.

Data Conclusion

4D flow MRI with self‐navigation was technically feasible, showing promise in quantifying the hemodynamic effects of cirrhosis. Proposed quantitative metrics of hepatic vascular resistance correlated with PSS.

Level of Evidence

3

Technical Efficacy Stage

2
Measurement‐based analysis of GaAs HEMT technologies: Multilayer D‐H pseudomorphic HEMT versus conventional S‐H HEMT
Authors: Alim Mohammad A. , Ali Mayahsa M. , Crupi Giovanni
Published: February 2021

The key objective of this study is to check out the performance of two multilayer processed double‐heterojunction pHEMTs with different gate width as well as one conventional single‐heterojunction HEMT. Different types of investigation have been undertaken by means of on‐wafer DC, small‐signal, and nonlinear two‐tone measurements. The modeling of the DC output characteristics was successfully accomplished using the FET's Curtice model for all of three tested devices. The main figures of merit for microwave and millimeter wave applications have been determined from scattering parameter measurements and then discussed in detail. Furthermore, to attain a better insight of the device behavior, the nonlinear intermodulation distortion behavior has been also studied and compared for the three devices over different bias conditions. A careful analysis of the DC and RF characteristics over a wide range of working conditions is necessary to ensure adequate transistor operation, depending on the given application of interest.
Numerical modeling of the responses of soil temperature and soil moisture to climate change over the Tibetan Plateau, 1961–2010
Authors: Fang Xuewei , Luo Siqiong , Lyu Shihua , Cheng Chen , Li Zhaoguo , Zhang Shaobo
Published: February 2021

Changes in soil temperature (ST) and soil moisture (SM) are essential for climate change and ecosystem assessments. Previous investigations on the ST and SM on the Tibetan Plateau (TP) are mainly based on the situ observation and the satellite products. In this study, the improved Community Land Model version 4.5 (CLM4.5), with proper parameter optimization and surface datasets update, is used to estimate the response of ST and SM in the TP to climate change in the long‐term time series from 1961 to 2010. After validating the reasonability of the simulated results using the observations, the spatial distribution of changes in ST and SM in annual and seasonal time series since 1960s, 1980s, 1990s, are investigated respectively and the changes of precipitation (Pr) and surface evaporation (Ev) are also analysed to understand the cause of changes objectively. As a whole, the soil was warming and wetting at the maximum value of 0.31°C/decade and 0.77%/decade since the 1960s. However, the warming process in soil mainly occurred in the 1980s while the wetting tendency is detected since the 1990s extensively. Except for the influence of air warming, the enhanced Pr and Ev might also be indispensable factors that caused the intensive wetting process but damped warming process in soil. Summer is the favourable season for the thermal and hydraulic variation since the 1980s. There exists the striking warmer and drier trend in the eastern TP since 1980s while the colder and wetter condition in the western TP since the 1990s. The magnitude of variation in soil is magnified from 1990s under the continuing impact of climate change.
Evaluating the meteorological drought characteristics over Pakistan using in situ observations and reanalysis products
Authors: Ullah Irfan , Ma Xieyao , Yin Jun , Asfaw Temesgen Gebremariam , Azam Kamran , Syed Sidra , Liu Mengyang , Arshad Muhammad , Shahzaman Muhammad
Published: February 2021

Drought is one of the most frequent natural disasters occurring in Pakistan and has a great influence on livelihood, agriculture, and economy. The availability of long‐term high‐quality reanalysis products over Pakistan has been of great concern in recent decades. Here, we conduct drought assessment in Pakistan based on the standardized precipitation index (SPI) and the standardized precipitation evapotranspiration index (SPEI) at 3, 6, and 12 months timescales during 1983–2018. We use long‐term in situ observations to evaluate the accuracy of reanalysis products, including Climatic Research Unit (CRU TS), National Centers for Environmental Prediction version II (NCEP‐2), European Centre for Medium‐Range Weather Forecasts Version‐5 (ERA‐5), and Modern‐Era Retrospective analysis for Research and Applications version II (MERRA‐2). The main results are summarized as follows: (a) drought indices and drought areas assessed from reanalysis products are relatively more representative of historical droughts that had occurred in southern Pakistan and overestimation is evident for drought severity in western than eastern Pakistan; (b) statistically significant increasing trends (1984–1998 and 2000–2010) in monthly drought areas and occurrence are evident by CRU TS and MERRA‐2 in dominant arid and semiarid regions; (c) climate variables and drought features of southern Pakistan are best represented by CRU TS and MERRA‐2, while that of southwestern and western parts are best represented by ERA‐5; (d) the Nash–Sutcliffe efficiency (NSE) results range from −2 to 1, where the NSE of SPEI values (−1.0) show relatively weaker than SPI values (0.5) in most parts of the regions, specifically in the southern Pakistan; (e) a strong positive linear relationship on a monthly scale is evident in CRU TS, MERRA‐2, and ERA‐5 exhibiting relatively high correlation coefficient (0.84), except for NCEP‐2. Furthermore, the SPEI results are found to be better than SPI; thus, this study suggests SPEI may be more suitable than SPI in monitoring droughts under climate change.
Changes in summer precipitation variability in central Brazil over the past eight decades
Authors: Prado Luciana Figueiredo , Wainer Ilana , Yokoyama Elder , Khodri Myriam , Garnier Jeremie
Published: February 2021

Central Brazil hydroclimate is in the core region of the South American monsoon system. Thus, understanding precipitation variability in this area is crucial not only for the prediction of extreme events such as droughts and floods, but also for water resources management. Ocean teleconnections influence central Brazil precipitation from intraseasonal to interdecadal frequencies, in both linear and nonlinear ways, mainly during the austral summer. Pacific Ocean climate modes can influence South American precipitation, but how its variability changes over time is still a theme of scientific debate. Here we examined the influence of Pacific variability on summer precipitation in central Brazil during the last eight decades. We applied nonparametric spectral methods to four different observational datasets, and to AMIP‐type precipitation outputs from the Laboratoire de Météorologie Dynamique zoom model (LMDZ) in Coupled Model Intercomparison Project phases 5 and 6 (CMIP5 and CMIP6) contributions of the Institut Pierre Simon Laplace (IPSL) coupled model. Our results showed an increase in amplitude and frequency of summer precipitation variability after the 1970s climate transition. Spectral analysis associated these changes to a transition in Pacific Ocean influence to central Brazil precipitation, from PDO‐ to El Niño–Southern Oscillation (ENSO)‐related variability after the 1970s climate transition. Composite analysis suggests these changes are related to teleconnection patterns between the Pacific Ocean and South America precipitation.
Trends in the occurrence of pan‐Arctic warm extremes in the past four decades
Authors: Yu Lejiang , Zhong Shiyuan , Sun Bo
Published: February 2021

The most recent historic heat wave in Siberia with record‐shattering temperatures is a reflection that, as a manifestation of global warming, the Arctic is experiencing more frequent and severe warm‐temperature extremes that could have global consequences. Here, we apply the self‐organizing map (SOM) clustering method to 6‐hr data from ERA‐Interim from 1979 to 2017 to document the spatial and seasonal variations of the trends in the number of warm‐extreme days over the pan‐Arctic region, and to apportion the trends into a dynamic component representing changes in atmospheric circulation patterns, a thermodynamic component not directly related to circulations, and an interaction component. We show significant upward trends in the occurrence of warm extremes across much of the Arctic Ocean in all seasons except for summer when regions of significant upward trends move from the Arctic Ocean to the Canadian Arctic Archipelago, Greenland, and the northern North Atlantic. The direction and magnitude of the trends in seasonal warm extremes as well as their seasonal and spatial variations are dominated by the thermodynamic component, with the dynamic component and the interaction component at least an order of magnitude smaller. Although negligible to the long‐term, pan‐Arctic averaged trend, the dynamic component may be comparable with, or even larger than, the thermodynamic component at some locations and under certain atmospheric circulation patterns.