bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly stable metal-organic framework UiO-66-NH2 for high-performance triboelectric nanogenerators
Authors: Wang Yong-Mei , Zhang Xinxin , Yang Dingyi , Wu Liting , Zhang Jiaojiao , Lei Tianmin , Yang Rusen
Published: October 2021

The high porosity, controllable size, high surface area, and chemical versatility of a metal-organic framework (MOF) enable it a good material for a triboelectric nanogenerator (TENG), and some MOFs have been incorporated in the fabrication of TENGs. However, the understanding of effects of MOFs on the energy conversion of a TENG is still lacking, which inhibits the improvement of the performance of MOF-based TENGs. Here, UiO-66-NH2 MOFs were found to significantly increase the power of a TENG and the mechanism was carefully examined. The electron-withdrawing (EW) ability of Zr-based UiO-66-family MOFs was enhanced by designing the amino functionalized 1,4-terephthalic acid (1,4-BDC) as ligand. The chemically modified UiO-66-NH2 was found to increase the surface roughness and surface potential of a composite film with MOFs embedded in polydimethylsiloxane (PDMS) matrix. Thus the total charges due to the contact electrification increased significantly. The composite-based TENG was found to be very durable and its output voltage and current were 4 times and 60 times higher than that of a PDMS-based TENG. This work revealed an effective strategy to design MOFs with excellent EW abilities for high-performance TENGs.
Ge2Sb2Te5-based nanocavity metasurface for enhancement of third harmonic generation
Authors: Li Yang , Zhang Xuecai , Tang Yutao , Cai Wenfeng , Liu Kuan , Mao Ningbin , Li Kingfai , Deng Junhong , Liu Yanjun , Cao Tun , Li Guixin
Published: October 2021

The third-order nonlinear processes in nanophotonic devices may have great potentials for developing ultra-compact nonlinear optical sources, ultrafast optical switches and modulators, etc. It is known that the performance of the nonlinear nanophotonic devices strongly relies on the optical resonances and the selection of appropriate nonlinear materials. Here, we demonstrate that the third harmonic generations (THG) can be greatly enhanced at subwavelength scale by incorporating α-Ge2Sb2Te5 (α-GST) into the nanocavity metasurface. Under pumping of a near-infrared femtosecond laser, the THG from the nanocavity metasurface is ∼50 times stronger than that from the bare GST planar film. In addition, the nanocavity metasurface also provides a powerful platform for characterizing the third-order nonlinear susceptibility of the active medium in the cavity. We expect that the GST-based nanocavity metasurface could open new routes for achieving high efficiency nonlinear nanophotonic devices.
Preferences of Persons With or at Risk for Hepatitis C for Long-Acting Treatments
Authors: Weld Ethel D , Astemborski Jacqueline , Kirk Gregory D , Sulkowski Mark S , Katz Stephanie , Rothman Richard , Solomon Sunil S , Matthews Gail V , Hsieh Yu Hsiang , Verma Malvika , Traverso Giovanni , Swindells Susan , Owen Andrew , Feld Jordan , Flexner Charles , Mehta Shruti H , Thomas David L
Published: October 2021

Background

Whereas safe, curative treatments for hepatitis C virus (HCV) have been available since 2015, there are still 58 million infected persons worldwide, and global elimination may require new paradigms. We sought to understand the acceptability of approaches to long-acting HCV treatment.

Methods

A cross-sectional, 43-question survey was administered to 1457 individuals with or at risk of HCV at 28 sites in 9 countries to assess comparative interest in a variety of long-acting strategies in comparison with oral pills.

Results

Among HCV-positive participants, 37.7% most preferred an injection, 5.6% an implant, and 6% a gastric residence device, as compared with 50.8% who stated they would most prefer taking 1–3 pills per day. When compared directly to taking pills, differences were observed in the relative preference for an injection based on age (P<.001), location (P<.001), and prior receipt of HCV treatment (P=.005) but not sex. When an implant was compared with pills, greater preference was represented by women (P=.01) and adults of younger ages (P=.01 per 5 years). Among participants without HCV, 49.5% believed that injections are stronger than pills and 34.7% preferred taking injections to pills. Among those at-risk participants who had received injectable medications in the past, 123 of 137 (89.8%) expressed willingness to receive one in the future.

Conclusions

These data point to high acceptability of long-acting treatments, which for a substantial minority might even be preferred to pills for the treatment of HCV infection. Long-acting treatments for HCV infection might contribute to global efforts to eliminate hepatitis C.
Translation of MT-ATP6 pathogenic variants reveals distinct regulatory consequences from the co-translational quality control of mitochondrial protein synthesis
Authors: Ng Kah Ying , Richter Uwe , Jackson Christopher B , Seneca Sara , Battersby Brendan J
Published: October 2021

Pathogenic variants that disrupt human mitochondrial protein synthesis are associated with a clinically heterogeneous group of diseases. Despite an impairment in oxidative phosphorylation being a common phenotype, the underlying molecular pathogenesis is more complex than simply a bioenergetic deficiency. Currently, we have limited mechanistic understanding on the scope by which a primary defect in mitochondrial protein synthesis contributes to organelle dysfunction. Since the proteins encoded in the mitochondrial genome are hydrophobic and need co-translational insertion into a lipid bilayer, responsive quality control mechanisms are required to resolve aberrations that arise with the synthesis of truncated and misfolded proteins. Here, we show that defects in the OXA1L-mediated insertion of MT-ATP6 nascent chains into the mitochondrial inner membrane are rapidly resolved by the AFG3L2 protease complex. Using pathogenic MT-ATP6 variants, we then reveal discrete steps in this quality control mechanism and the differential functional consequences to mitochondrial gene expression. The inherent ability of a given cell type to recognize and resolve impairments in mitochondrial protein synthesis may in part contribute at the molecular level to the wide clinical spectrum of these disorders.
Dark Energy Survey Year 3 results: galaxy sample for BAO measurement
Authors: Rosell A Carnero , Rodriguez-Monroy M , Crocce M , Elvin-Poole J , Porredon A , Ferrero I , Mena-Fernández J , Cawthon R , De Vicente J , Gaztanaga E , Ross A J , Sanchez E , Sevilla-Noarbe I , Alves O , Andrade-Oliveira F , Asorey J , Avila S , Brandao-Souza A , Camacho H , Chan K C , Ferté A , Muir J , Riquelme W , Rosenfeld R , Cid D Sanchez , Hartley W G , Weaverdyck N , Abbott T , Aguena M , Allam S , Annis J , Bertin E , Brooks D , Buckley-Geer E , Burke D , Calcino J , Carollo D , Kind M Carrasco , Carretero J , Castander F , Choi A , Conselice C , Costanzi M , da Costa L , da Silva Pereira M E , Davis T , Desai S , Diehl H T , Doel P , Drlica-Wagner A , Eckert K , Everett S , Evrard A , Flaugher B , Fosalba P , Frieman J , Garcia-Bellido J , Gerdes D , Giannantonio T , Glazebrook K , Gruen D , Gruendl R , Gschwend J , Gutierrez G , Hinton S , Hollowood D , Honscheid K , Hoyle B , Huterer D , James D , Kim A , Krause E , Kuehn K , Lahav O , Lewis G , Lidman C , Lima M , Maia M , Malik U , Marshall J , Menanteau F , Miquel R , Mohr J , Moller A , Morgan R , Ogando R , Palmese A , Paz-Chinchon F , Percival W , Pieres A , Malagón A Plazas , Roodman A , Scarpine V , Schubnell M , Serrano S , Sharp R , Sheldon E , Smith M , Soares-Santos M , Suchyta E , Swanson M , Tarle G , Thomas D , To C , Tucker B , Tucker D , Uddin S , Varga T N ,   DES Collaboration
Published: October 2021

In this paper, we present and validate the galaxy sample used for the analysis of the baryon acoustic oscillation (BAO) signal in the Dark Energy Survey (DES) Y3 data. The definition is based on a colour and redshift-dependent magnitude cut optimized to select galaxies at redshifts higher than 0.5, while ensuring a high-quality determination. The sample covers ${\sim }\, 4100$ deg2to a depth of i = 22.3 (AB) at 10σ. It contains 7031 993 galaxies in the redshift range from $z$ = 0.6 to 1.1, with a mean effective redshift of 0.835. Redshifts are estimated with the machine learning algorithm dnf, and are validated using the VIPERS PDR2 sample. We find a mean redshift bias of $z_{\mathrm{bias}} {\sim }\, 0.01$ and a mean uncertainty, in units of 1 + $z$, of $\sigma _{68} {\sim }\, 0.03$. We evaluate the galaxy population of the sample, showing it is mostly built upon Elliptical to Sbc types. Furthermore, we find a low level of stellar contamination of $\lesssim 4{{\ \rm per\ cent}}$. We present the method used to mitigate the effect of spurious clustering coming from observing conditions and other large-scale systematics. We apply it to the BAO sample and calculate weights that are used to get a robust estimate of the galaxy clustering signal. This paper is one of a series dedicated to the analysis of the BAO signal in DES Y3. In the companion papers, we present the galaxy mock catalogues used to calibrate the analysis and the angular diameter distance constraints obtained through the fitting to the BAO scale.
Nucleosomes enter cells by clathrin- and caveolin-dependent endocytosis
Authors: Wang Huawei , Shan Xiajing , Ren Mengtian , Shang Mengdi , Zhou Chuanzheng
Published: October 2021

DNA damage and apoptosis lead to the release of free nucleosomes—the basic structural repeating units of chromatin—into the blood circulation system. We recently reported that free nucleosomes that enter the cytoplasm of mammalian cells trigger immune responses by activating cGMP-AMP synthase (cGAS). In the present study, we designed experiments to reveal the mechanism of nucleosome uptake by human cells. We showed that nucleosomes are first absorbed on the cell membrane through nonspecific electrostatic interactions between positively charged histone N-terminal tails and ligands on the cell surface, followed by internalization via clathrin- or caveolae-dependent endocytosis. After cellular internalization, endosomal escape occurs rapidly, and nucleosomes are released into the cytosol, maintaining structural integrity for an extended period. The efficient endocytosis of extracellular nucleosomes suggests that circulating nucleosomes may lead to cellular disorders as well as immunostimulation, and thus, the biological effects exerted by endocytic nucleosomes should be addressed in the future.
Protein lipoylation in mitochondria requires Fe–S cluster assembly factors NFU4 and NFU5
Authors: Przybyla-Toscano Jonathan , Maclean Andrew E , Franceschetti Marina , Liebsch Daniela , Vignols Florence , Keech Olivier , Rouhier Nicolas , Balk Janneke
Published: October 2021

Plants have evolutionarily conserved NifU (NFU)-domain proteins that are targeted to plastids or mitochondria. “Plastid-type” NFU1, NFU2, and NFU3 in Arabidopsis (Arabidopsis thaliana) play a role in iron–sulfur (Fe–S) cluster assembly in this organelle, whereas the type-II NFU4 and NFU5 proteins have not been subjected to mutant studies in any plant species to determine their biological role. Here, we confirmed that NFU4 and NFU5 are targeted to the mitochondria. The proteins were constitutively produced in all parts of the plant, suggesting a housekeeping function. Double nfu4 nfu5 knockout mutants were embryonic lethal, and depletion of NFU4 and NFU5 proteins led to growth arrest of young seedlings. Biochemical analyses revealed that NFU4 and NFU5 are required for lipoylation of the H proteins of the glycine decarboxylase complex and the E2 subunits of other mitochondrial dehydrogenases, with little impact on Fe–S cluster-containing respiratory complexes or aconitase. Consequently, the Gly-to-Ser ratio was increased in mutant seedlings and early growth improved with elevated CO2 treatment. In addition, pyruvate, 2-oxoglutarate, and branched-chain amino acids accumulated in nfu4 nfu5 mutants, further supporting defects in the other three mitochondrial lipoate-dependent enzyme complexes. NFU4 and NFU5 interacted with mitochondrial lipoyl synthase (LIP1) in yeast 2-hybrid and bimolecular fluorescence complementation assays. These data indicate that NFU4 and NFU5 have a more specific function than previously thought, most likely providing Fe–S clusters to lipoyl synthase.
Current Evidence on Prevention of Atrial Fibrillation: Modifiable Risk Factors and the Effects of Risk Factor Intervention
Authors: Akboga Mehmet Kadri , Inanc Ibrahim Halil , Keskin Muhammed , Sabanoglu Cengiz , Gorenek Bulent
Published: October 2021

Atrial fibrillation (AF) is one of the most encountered arrhythmias in clinical practice. It is also estimated that the absolute AF burden may increase by greater than 60% by 2050. It is inevitable that AF will become one of the largest epidemics in the world and may pose a major health problem for countries. Although AF rarely causes mortality in the acute period, it causes a significant increase in mortality and morbidity, including a fivefold increase in the risk of stroke, a twofold increase in dementia, and a twofold increase in myocardial infarction in the chronic period. Despite all the advances in the treatment of AF, it is better understood day by day that preventing AF may play a key role in reducing AF and its related complications. Modification of the main modifiable factors such as quitting smoking, abstaining from alcohol, changing eating habits, and exercise seems to be the first step in preventing AF. The strict adherence to the treatment process of secondary causes predisposing to AF such as DM, hypertension, obesity, and sleep apnea is another step in the prevention of AF. Both an individual approach and global public health campaigns can be highly beneficial to reduce the risk of AF. In this review, we aimed to summarize the current evidence on the relationship between modifiable risk factors and AF, and the impact of possible interventions on these factors in preventing or reducing the AF burden in the light of recently published guidelines and studies.
Update in palliative care in gynecologic oncology
Authors: Karlin Daniel , Khoo Teresa , Pietras Christopher
Published: October 2021

Purpose of review

This review summarizes research advances in quality of life, symptom management, and end-of-life practices within palliative care that can benefit patients with gynecologic cancers.

Recent findings

Addressing fertility issues, sexual side effects, and possible disease recurrence can promote quality of life in gynecologic cancer survivors. Cannabis can provide some benefit for nausea and neuropathic pain, yet for nonneuropathic pain presentations, it does not appear to provide significant benefit in reducing opioid usage. Lastly, palliative care outcomes, such as reduced aggressive care at the end of life and higher rates of hospice enrollment are augmented by the presence of an outpatient palliative care clinic.

Ongoing advances in palliative care research hold potential for improvement in systems delivery of palliative care as well as symptom management and psychosocial support.
When is enough, enough? Exploring ethical and team considerations in paediatric cardiac care dilemmas
Authors: Lynch Aine , Kirsch Roxanne
Published: October 2021

Purpose of review

Therapies for paediatric congenital and acquired heart disease continue to evolve and the appropriateness of pursuing life sustaining interventions at margins of standard therapy is ethically challenging.

Recent findings

With ongoing emphasis on shared decision making, recent literature explored physician and parental perspectives on communication with families and offering interventions for complex congenital heart disease and advanced heart failure. The inclusion of parental values and views in this process is now widely accepted. Identified outstanding challenges include difficulty with prognostication from the outset, adjusting long-term goals of care to changes in clinical parameters, need for consistency in communication including regular review meetings with family or surrogate decision-makers. Bioethics consultation and multidisciplinary team reviews may be helpful supports. Palliative care involvement in this population improves quality of life and alleviates parental distress but this collaboration is not optimized.

Decision to offer, forgo, or discontinue life-sustaining therapies for children with heart disease has nuanced and context-specific considerations, and must integrate burdens of interventions with patient and family values. Thus, decision making remains complex and demands thoughtful review of not only risks and benefits, but views and values, clearly communicated to team and family.
The emerging role of cardiac contractility modulation in heart failure treatment
Authors: Chinyere Ikeotunye R. , Balakrishnan Mahesh , Hutchinson Mathew D.
Published: October 2021

Purpose of review

Heart failure often progresses despite optimal medical and device therapies, and advanced mechanical circulatory support has limited availability and substantial associated morbidity. Cardiac contractility modulation (CCM) provides nonexcitatory stimulation to ventricular myocardium which increases cardiac contractility without increasing oxygen demand. This review describes the emerging role of CCM in heart failure treatment.

Recent findings

The FIX-HF-5C2 study demonstrated similar safety and efficacy profile of the two-lead Optimizer device in comparison with the prior three-lead system, thereby decreasing procedural complexity and minimizing endocardial hardware. The FIX-HF-5C trial underscored the benefit of CCM in patients with mild-moderate left ventricular dysfunction (ejection fraction, 25–45%) with New York Heart Association (NYHA) Class III symptoms. The summarized randomized trial data show consistent improvements in peak VO2, 6-min walk distance, and NYHA functional class with CCM. Future trials are planned to determine the role of CCM in heart failure patients with preserved ejection fraction, obligate ventricular pacing, and atrial arrhythmias.

Nonexcitatory extracellular electric potentials can facilitate inotropic improvements in the failing heart. The mechanism of CCM does not increase myocardial oxygen consumption and has been shown to mitigate heart failure symptoms, decrease hospitalizations, and work in synergy with guideline-directed therapy for heart failure.
Reduction in Medication Refill Encounters Through Primary Care Redesign Workflow Changes
Authors: Swedlund Matthew , Kamnetz Sandra , Birstler Jen , Trowbridge Elizabeth , Arndt Brian , Micek Mark , Lochner Jennifer , Pandhi Nancy
Published: October 2021

With a goal of improving efficiency and reducing workload outside of visits, we sought to examine a primary care redesign process aimed at reducing refill requests made outside of office visits. Data on the number of refill encounters per panel member were collected at 17 clinics before, during, and after the implementation of a redesign process. There was an initial reduction in the number of medication refill encounters, and the rate of refill encounters continued to decline following implementation. Variation across clinic contexts suggests that redesign processes may need to be tailored for different settings to optimize effectiveness.
Naive haemophilia mice displayed different pattern of cytokine profiles of cytokine profiles changes might be associated with subclinical bleeding
Authors: Zhang Feixu , Zong Xiaoying , Zhou Xinyue , Sun Shuming , Xiao Xiao , Sun Junjiang
Published: October 2021

Subclinical bleeding is a haemorrhage event not clinically detected in haemophilia, and no reliable method is available for predicting subclinical bleeding. We investigated whether haemophilia mice have subclinical haemorrhage and evaluated potential biomarkers including multiple cytokine changes to predict subclinical haemorrhage. Plasma from naïve FVIII−/− and FIX−/− mice and their wild-type counterparts (FVIII WT and FIX WT, respectively) were measured for prothrombin fragment 1 + 2 (F1 + 2) and multiple cytokines. Haemophilia mice with induced hemarthrosis were used as positive clinical bleeding controls. Naive haemophilia mice that displayed higher levels than positive bleeding control were counted. Univariate and multivariate analyses of cytokines were performed. Compared with wild-type mice (FVIII WT 1.1–6.2 vs. FIX WT 2.7–6.7 pmol/l), F1 + 2 widely varied in both haemophilia mouse strains (FVIII−/− 3.7–25.7 vs. FIX−/− 2.7–15.7 pmol/l). Each cytokine varied widely in both naive haemophilia A and B mice, but not significantly, for most cytokines. In comparison to haemophilia mice with hemarthrosis bleeding challenge, naive FVIII−/− mice had elevated pro-inflammatory cytokines and FIX−/− mice had elevated anti-inflammatory cytokines. In addition, interleukin (IL)-4, followed by IL-1, IL-6, TNF-α and MIP-1α in FVIII−/− mice and MIP-1α, followed by IL-1, IL-10 in FVIII−/− mice exhibited significant differences potentially associated with potential subclinical bleeding. Naive haemophilia mice showed elevated pro-inflammatory cytokines with different patterns, represented by pro-inflammatory cytokine elevation in more naïve FVIII−/− mice and more anti-inflammatory cytokines in FIX−/− mice.
CHA2DS2-VASc score in patients with COVID-19 pneumonia and its relationship with biomarkers of thrombosis, inflammation and myocardial injury
Authors: Arcari Luca , Luciani Michelangelo , Cacciotti Luca , Musumeci Maria Beatrice , Spuntarelli Valerio , Bentivegna Enrico , Camastra Giovanni , Ansalone Gerardo , Santini Claudio , Martelletti Paolo , Volpe Massimo , De Biase Luciano
Published: October 2021

CHA2DS2-VASC score associates with worse prognosis in coronavirus-disease-19 (COVID-19). This study investigated laboratory correlates of increasing CHA2DS2- VASc in patients with COVID-19. Patients with COVID-19 were stratified by CHA2DS2-VASc (Group 1: CHA2DS2-VASc 0-1; Group 2: CHA2DS2-VASc 2-3; Group 3: CHA2DS2-VASc ≥4). We found stepwise increase of D-dimer, hs-Troponin and in-hospital mortality across groups (all P < 0.01). D-dimer and hs-Troponin remained independently associated with CHA2DS2-VASc (B = 0.145, P = 0.03; B = 0.320, P < 0.001, respectively). We found significant correlations between D-dimer and C-reactive protein (CRP) in Group 1 and 2, not in Group 3 (r
2 = 0.103, P = 0.005; r

2
 = 0.226, P = 0.001; r

2
 = 0.021, P = 0.253 respectively), and between D-dimer and hs-Troponin in group 2 and 3, not in Group 1 (r
2 = 0.122, P = 0.003; r
2 = 0.120, P = 0.007; r
2 = 0.006, P = 0.514 respectively). In our cohort, CHA2DS2- VASc was independently associated with D-dimer and hs- Troponin increase. Variable relationships of D-dimer with hs-Troponin and CRP within different CHA2DS2-VASc strata suggest multiple mechanisms to be responsible for D-dimer increase in COVID-19.
The hepatitis C cascade of care in HIV/hepatitis C virus coinfected individuals in Europe: regional and intra-regional differences
Authors: Fursa Olga , Mocroft Amanda , Lazarus Jeffrey V. , Amele Sarah , Lundgren Jens , Matulionyte Raimonda , Rasmussen Line D. , Rockstroh Jürgen K. , Parczewski Milosz , Jilich David , Moreno Santiago , Vassilenko Anna , Lacombe Karine , Wandeler Gilles , Borodulina Elena , Brännström Johanna , Wiese Lothar , Orkin Chloe , Behrens Georg M.N. , Mansinho Kamal , Portu Jose Joaquin , Peters Lars
Published: October 2021

Background:

Following the introduction of direct-acting antiviral therapy in 2013, WHO launched the first Global Health Sector Strategy on Viral Hepatitis. We describe a hepatitis C virus (HCV) cascade of care in people with HIV (PWH) across Europe in terms of reaching the WHO elimination targets of diagnosing 90% and treating 80% of HCV-infected individuals.

Methods:

HIV/HCV-coinfected participants in the EuroSIDA cohort under prospective follow-up at October 1, 2019, were described using a nine-stage cascade of care. Care cascades were constructed across Europe, on a regional (n = 5) and country (n = 21) level.

Results:

Of 4773 anti-HCV positive PWH, 4446 [93.1%, 95% confidence interval (CI) 92.4–93.9)] were ever tested for HCV RNA, and 19.0% (95% CI 16.4–21.6) were currently HCV RNA positive, with the highest prevalence in Eastern and Central-Eastern Europe (33.7 and 29.6%, respectively). In Eastern Europe, 78.1% of the estimated number of chronic infections have been diagnosed, whereas this proportion was above 95% in the other four regions. Overall, 3116 persons have ever started treatment (72.5% of the ever chronically infected, 95% CI 70.9–74.0) and 2404 individuals (55.9% of the ever chronically infected, 95% CI 53.9–57.9) were cured. Cure proportion ranged from 11.2% in Belarus to 87.2% in Austria.

Conclusion:

In all regions except Eastern Europe, more than 90% of the study participants have been tested for HCV-RNA. In Southern and Central-Western regions, more than 80% ever chronically HCV-infected PWH received treatment. The proportion with cured HCV infection did not exceed 80% in any region, with significant heterogeneity between countries.

In a pan-European cohort of PWH, all regions except Eastern Europe achieved the WHO target of diagnosing 90% of chronic HCV infections, while the target of treating 80% of eligible persons was achieved in none of the five regions.
Parametric Multi-Scale Modeling of the Zygomaticus Major and Minor: Implications for Facial Reanimation
Authors: Peer Munawar , Tran John , Li Zhi , Fattah Adel Y. , Agur Anne M.R. , Davies Joel C.
Published: October 2021

Facial paralysis can severely impact functionality and mental health. Facial reanimation surgery can improve facial symmetry and movement. Zygomaticus minor (Zmin) and zygomaticus major (Zmaj) are 2 important perioral muscles, that function to elevate the upper lip, contributing to the formation of a smile. The objective of this study was to analyze the morphology in three-dimensional (3D) and quantify architectural parameters of Zmin and Zmaj. In ten formalin-embalmed specimens, Zmin and Zmaj were serially dissected and digitized at the fiber bundle level. The 2 muscles were modeled in 3D to construct high fidelity models. The 3D models were used to assess muscle morphology and quantify architectural parameters including mean fiber bundle length, physiological cross-sectional area, and line of action. Zygomaticus minor fiber bundles were oriented horizontally or slightly obliquely and had a muscular attachment to the medial modiolus. Zygomaticus minor was found to either have no partitions or medial and lateral partitions. Specimens with partitions were divided into type 1 and type 2. Type 1 consisted of a medial partition with fiber bundles attaching to the zygomatic bone at the inferior margin of the orbit. The type 2 medial partition attached to the lateral margin of the orbit to attach to the zygomatic bone. Zygomaticus major had obliquely oriented fiber bundles with most specimens having inferior and superior partitions attaching to the inferior aspect of the zygomatic bone. Zygomaticus major was found to have a greater mean fiber bundle length and physiological cross-sectional area than Zmin. The direction of the line of action of Zmin and Zmaj was closely related to fiber bundle arrangement. Detailed 3D anatomical understanding of Zmin and Zmaj, at the fiber bundle level, is critical for reconstructive surgeons performing dynamic facial reanimation. This data can be used to assist with selecting the ideal donor site for reconstruction.
Effectiveness of educational intervention on breast cancer knowledge and breast self-examination among female university students in Bangladesh: a pre-post quasi-experimental one group study
Authors: Sarker Rumpa , Islam Md. Saiful , Moonajilin Mst. Sabrina , Rahman Mahmudur , Gesesew Hailay Abrha , Ward Paul R
Published: October 2021

Background

Breast cancer is a global health issue and a leading cause of death among women. Early detection through increased awareness and knowledge on breast cancer and breast cancer screening is thus crucial. The aim of the present study was to assess the effect of educational intervention program on breast cancer knowledge and practice of breast self-examination among young female students of a university in Bangladesh.

Methods

A quasi-experimental one group (pre-post) study design was conducted at Jahangirnagar University in Bangladesh. Educational information on breast cancer and breast self-examination (BSE), demonstration of BSE procedure and leaflets were distributed among 400 female students in common room setting in dormitories after obtaining written informed consent. The stepwise procedures of BSE performance were demonstrated with images. Pre-intervention and 15 days post-intervention assessments were conducted to assess the changes in knowledge on breast cancer and practices of BSE. Mc-Nemar’s tests and paired sampledt-tests were performed to investigate the differences between pre- and post-test stages.

Results

Significant changes were found in knowledge and awareness about breast cancer and BSE practices after the educational session. The significant differences were measures in the mean scores of pre-test vs. post-test: breast cancer symptoms (2.99±1.05 vs. 6.35±1.15;p<0.001), risk factors (3.35±1.19 vs. 7.56±1.04;p<0.001), treatment (1.79±0.90 vs. 4.63±0.84;p<0.001), prevention (3.82±1.32 vs. 7.14±1.03;p<0.001), screening of breast cancer (1.82±0.55 vs. 3.98±0.71;p<0.001) and process of breast self-examination (1.57±1.86 vs. 3.94±0.93;p<0.001). Likewise, a significate percentage of change in BSE practices was obtained between pre-test and post-test (21.3% vs. 33.8%;p<0.001)

Conclusions

This study findings confirm that the study population had poor awareness and knowledge at baseline that was improved significantly after educational session. A nationwide reach-out with community-based interventions is recommended for female population in both rural and urban areas.
Effects of cognitive behavioral therapy for insomnia on subjective and objective measures of sleep and cognition
Authors: Perrault Aurore A. , Pomares Florence B. , Smith Dylan , Cross Nathan E. , Gong Kirsten , Maltezos Antonia , McCarthy Margaret , Madigan Emma , Tarelli Lukia , McGrath Jennifer , Savard Josée , Schwartz Sophie , Gouin Jean-Philippe , Dang-Vu Thien Thanh
Published: October 2021

Study Objectives

To assess the effects of Cognitive Behavioral Therapy for insomnia (CBTi) on subjective and objective sleep, sleep-state misperception as well as self-reported and objective cognitive performance.

Methods

We performed a randomized controlled trial with a treatment group and a wait-list control group to assess changes in insomnia symptoms after CBTi (8 sessions/3 months) in 62 participants with chronic insomnia. To this end, we conducted a multimodal investigation of sleep and cognition including subjective measures of sleep difficulties (Insomnia Severity Index (ISI), sleep diaries) and cognitive functioning (Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire), objective assessments of sleep (polysomnography recording, cognition (attention and working memory tasks), and sleep-state misperception measures, collected at baseline and at 3-months post-randomization. At 6 months post-randomization, we collected similar data from the wait-list group after CBTi. We also assessed ISI one year after CBTi in both groups. Our main analysis investigated changes in sleep and cognition after 3 months (treatment versus wait-list group). In secondary analyses, we pooled data from both groups to observe changes after CBTi.

Results

ISI score was reduced and self-reported sleep quality improved after CBTi (treatment group at 3 months and pooled groups after CBTi). Sleep misperception in sleep onset latency and sleep duration decreased after CBTi. In contrast, objective sleep, objective and subjective cognitive functioning did not improve after CBTi.

Conclusions

We showed that CBTi has a beneficial effect on variables pertaining to the subjective perception of sleep, which is a central feature of insomnia. However, we observed no significant effect of CBTi on measures of cognitive functioning.

STATEMENT OF SIGNIFICANCE

Nighttime sleep difficulties and daytime cognitive impairment are the two main complaints of individuals suffering from insomnia. We investigated the effects of Cognitive Behavioral Therapy for insomnia (CBTi) on these two aspects of chronic insomnia, using both self-reported and objective measures, as well as sleep-state misperception (i.e., the discrepancy between self-reported and objective sleep). We showed significant changes after CBTi in insomnia severity, subjective sleep quality and perception of sleep, while no consistent benefit emerged for objective measures of sleep and assessments of cognitive functioning. CBTi thus appears to primarily benefit subjective sleep quality as well as the alignment between subjective and objective estimates of sleep.
Association of lipid-regulating drugs with dementia and related conditions: an observational study of data from the Clinical Practice Research Datalink
Authors: McGuinness Luke A , Higgins Julian PT , Walker Venexia M , Davies Neil M , Martin Richard M , Coulthard Elizabeth , Davey-Smith George , Kehoe Patrick G , Ben-Shlomo Yoav
Published: October 2021

2

Background

There is some evidence that circulating blood lipids play a role in the development of Alzheimer’s disease (AD) and dementia. These modifiable risk factors could be targeted by existing lipid-regulating agents, including statins, for dementia prevention. Here, we test the association between lipid-regulating agents and incidence of dementia and related conditions in the Clinical Practice Research Datalink (CPRD), an United Kingdom-based electronic health record database.

Methods

A retrospective cohort study was performed using routinely collected CPRD data (January 1995 and March 2016). Multivariable Cox proportional hazard models, allowing for a time-varying treatment indicator, were used to estimate the association between seven lipid-regulating drug classes (vs. no drug) and five dementia outcomes (all-cause, vascular and other dementias, and probable and possible Alzheimer’s disease).

Results

We analyzed 1,684,564 participants with a total follow-up of 10,835,685 patient-years (median: 5.9 years (IQR:2.7-9.7)). We found little evidence that lipid-regulating agents were associated with incidence of Alzheimer’s disease (probable HR:0.98, 95%CI:0.94-1.01; possible HR:0.97, 95%CI:0.93-1.01), but there was evidence of an increased risk of all-cause (HR:1.17, 95%CI:1.14-1.19), vascular (HR:1.81, 95%CI:1.73-1.89) and other dementias (HR:1.19, 95%CI:1.15-1.24). Evidence from a number of control outcomes indicated the presence of substantial residual confounding by indication (ischaemic heart disease HR: 1.62, 95%CI: 1.59-1.64; backpain HR: 1.04, 95%CI: 1.03-1.05; and Type 2 diabetes HR: 1.50, 95%CI: 1.48-1.51).

Conclusion

Lipid-regulating agents were not associated with reduced Alzheimer’s disease risk. There was some evidence of an increased the risk of all-cause, vascular and other dementias, likely due to residual confounding by indication.

3

Key messages

A large cohort of patients from the Clinical Practice Research Datalink (CPRD) electronic health record database was assembled to examine the association of lipid-regulating agents, such as statins, with dementia outcomes.

There was little evidence that lipid-regulating agents were associated with Alzheimer’s disease, but there was some evidence for a harmful association with all-cause, vascular and other dementias. In all cases, the estimated associations were driven by the any statin subgroup, which comprised most participants in our cohort.

Evidence from the control outcome analyses indicated strong residual confounding by indication, mostly likely related to vascular factors.
Prediction and predictor elucidation of the onset of metabolic syndrome among young workers using machine learning techniques: A nationwide study in Japan
Authors: Suda Miyuki , Ooka Tadao , Yamagata Zentaro
Published: October 2021

Objectives

Predictive models for the onset of metabolic syndrome (MS) among people in their 30s are scarce. This study aimed to construct a highly accurate model to predict MS onset by age 40 years and to identify the important predictors of MS onset using health checkup data of Japanese company employees aged 30 and 35.

Methods

The study included 6,048 Japanese employees aged 40 years who had undergone periodic health examinations over 10 years. We developed prediction models for MS onset using machine learning methods including the random forest and logistic regression, and evaluated the models using the receiver operating characteristics and precision-recall curves. For the random forest models, the variable importance of each explanatory variable was calculated to identify important predictors of MS onset.

Results

The random forest had higher predictive power than logistic regression in all models, although the differences were non-significant. Regarding important predictors, diastolic blood pressure was the most important predictor of MS onset for men aged 30 and 35 years, while body mass index was the most important predictor for women aged 30 and 35 years.

Conclusions

We created a machine learning model to predict MS onset at age 40 with high accuracy from health examination data obtained at ages 30 or 35. Sex differences in important predictors of MS onset was shown by the variable importance indices of the random forest. Applying our model in routine healthcare management should provide early and appropriate health interventions to prevent MS onset in young people.
COVID-19 Prevention Facilitators and Barriers among Specific Ethnic Minority Communities in Rural Ohio
Authors: Pordell Paran , Ali Hammad , Martinez Gisela Medina , Taylor Brandi , Kondapally Karthik , Salehi Ellen , de Fijter Sietske , Hayes Nikki , Lloyd Spencer
Published: October 2021

Objective

To assess knowledge, beliefs, and behaviors concerning COVID-19 among Guatemalan, Marshallese, and Amish populations in rural Ohio; identify individual, interpersonal, community, and structural level challenges within each community; and provide population-specific recommendations to prevent and mitigate further SARS-CoV-2 transmission among these rural communities.

Methods

We conducted 30 key informant interviews in four rural counties in Ohio, in May 2020. Three teams of two investigators conducted interviews with local health department staff, community members, meat packing plant management, and community leaders from three communities disproportionately affected by the COVID-19 pandemic [Guatemalan (N=12), Marshallese (N=7), Amish (N=11)]. We used the Social Ecological Model to identify and categorize themes.

Results

Emerging and overall themes were identified and defined. Investigators identified COVID-19 knowledge gaps, myths, and misinformation, food insecurity, community cohesion, stigma, community culture and norms, lack of workplace safety policies, and access to testing as key themes to COVID-19 prevention.

Conclusions

Understanding specific barriers and identifying facilitators that most effectively provide resources, healthcare services, education, and social support tailored to specific communities would help deter SARS-CoV-2 transmission.
EXAMINING THE ROLE OF NON-SURGICAL THERAPY IN THE TREATMENT OF GERIATRIC INCONTINENCE
Authors: Parker-Autry Candace , Neiberg Rebecca , Leng X. Iris , Matthews Catherine A. , Dumoulin Chantale , Kuchel George , Kritchevsky Stephen B.
Published: October 2021

Objective

To examine the role of physical function impairments on the change in urinary incontinence symptoms after pelvic floor muscle training in older women.

Methods

This is a prospective cohort study of 70 community-dwelling women, older than 70 years, with at least moderate incontinence symptoms. A comprehensive assessment of pelvic floor and physical function was done at baseline. Individualized PFM training prescriptions with behavioral management strategies to reduce incontinence episodes were provided for 12 weeks. Baseline physical function was determined using the Short Physical Performance Battery (total score of ≤9/12 defined impairment). A 3-day bladder diary established daily incontinence episodes. The change in urinary incontinence episodes based on presence of physical function impairment was our primary outcome. Descriptive analyses compared important demographic and clinical characteristics. Longitudinal mixed model linear regression analyses were used to assess for change in incontinence and estimate of improvement based on the presence of physical function impairment adjusted for age, race, and BMI.

Results

Participants’ mean±SD age was 76.9±5.4 years and 15.7% were African American with no significant differences in age or race between groups. Women with physical function impairment had higher mean ± SD BMI (33.6±14.5 vs 27.4±5.8 kg/m2; p=0.03) and significantly greater baseline incontinence episodes (4.5±2.9 vs. 2.7±2.1 episodes/day; p=0.005) than in women without functional impairment, respectively. After 6 weeks of pelvic floor exercises, women with physical functional impairment had a non-significant decrease in incontinence episodes/day compared to women with normal physical function (mean [95%CI], −1.2 [−2.0,−0.5] vs −0.4 [−1.1, 0.3], p=0.31). Women with physical function impairments also reported lower improvement in their incontinence symptoms compared to women without functional impairment (50.7±5.9% vs 64.2±5.9%, p=0.08).

Conclusions

Non-surgical therapy to include pelvic floor muscle training may not significantly decrease urinary incontinence symptoms to a degree that is satisfactory in women older than 70 years seeking treatment for urinary incontinence.
Perceived Stress Among Faculty and First Year Students at a College of Pharmacy
Authors: Verdone Melinda , Murray Milena , Griffin Brooke , Arif Sally , Phillips Jennifer , Komperda Kathy , Winkler Susan , Gilchrist Annette
Published: October 2021

Purpose

Female faculty and students could be affected by stressors disproportionately compared to male counterparts, especially those with children or family obligations. A study was undertaken to determine: 1) stress levels of pharmacy faculty and first-year pharmacy students; 2) whether gender affected faculty and/or student stress levels disproportionally; and 3) how child and family care responsibilities influenced stress levels.

Methods

All first-year (P1) students enrolled in a College of Pharmacy were surveyed along with faculty. Stress levels were assessed using the Perceived Stress Scale (PSS10). Additional demographic information, including items related to children and family obligations, was collected.

Results

Faculty reported average perceived stress levels (M=15.50) while first-year students reported high perceived stress levels (M=21.14). Perceived stress levels of female faculty (M=16.43) were higher than those of male faculty (M=12.00). Perceived stress levels of female students (M=22.60) were higher than those of male students (M=16.78). Perceived stress levels of female faculty with younger children (M=18.85) were higher than those of male faculty with younger children (M=9.67). Perceived stress levels of female students with ≥10 hours of family obligations per week (M=22.71) were higher than male pharmacy students with ≥10 hours (M=12.80).

Conclusion

Lower levels of perceived stress for faculty compared to students may be due to the development of coping strategies coinciding with maturity. Results suggest more time spent on family obligations is negatively associated with stress levels for females, but not males. Colleges of pharmacy should invest resources to help reduce stress levels in faculty and student populations, particularly for the female gender.
Non-glycosylated Seipin to Cause a Motor Neuron Disease Induces ER stress and Apoptosis by Inactivating the ER Calcium Pump SERCA2b
Authors: Saito Shunsuke , Ishikawa Tokiro , Ninagawa Satoshi , Okada Tetsuya , Mori Kazutoshi
Published: October 2021

A causal relationship between endoplasmic reticulum (ER) stress and the development of neurodegenerative diseases remains controversial. Here, we focused on Seipinopathy, a dominant motor neuron disease, based on the finding that its causal gene product, Seipin, is a hairpin-like transmembrane protein in the ER. Gain-of-function mutations of Seipin produce non-glycosylated Seipin (ngSeipin), which was previously shown to induce ER stress and apoptosis at both cell and mouse levels albeit with no clarified mechanism. We found that aggregation-prone ngSeipin dominantly inactivated SERCA2b, the major calcium pump in the ER, and decreased the calcium concentration in the ER, leading to ER stress and apoptosis. This inactivation required oligomerization of ngSeipin and direct interaction of the ngSeipin C-terminus with SERCA2b, and was observed in Seipin-deficient human colorectal carcinoma-derived cells (HCT116) expressing ngSeipin at a level comparable with that in neuroblastoma cells (SH-SY5T). Our results thus provide a new direction to controversy noted above.
Compatibility logic of human enhancer and promoter sequences
Authors: Bergman Drew T. , Jones Thouis R. , Liu Vincent , Siraj Layla , Kang Helen Y. , Nasser Joseph , Kane Michael , Nguyen Tung H. , Grossman Sharon R. , Fulco Charles P. , Lander Eric S. , Engreitz Jesse M.
Published: October 2021

Gene regulation in the human genome is controlled by distal enhancers that activate specific nearby promoters. One model for the specificity of enhancer-promoter regulation is that different promoters might have sequence-encoded preferences for distinct classes of enhancers, for example mediated by interacting sets of transcription factors or cofactors. This “biochemical compatibility” model has been supported by observations at individual human promoters and by genome-wide measurements in Drosophila. However, the degree to which human enhancers and promoters are intrinsically compatible or specific has not been systematically measured, and how their activities combine to control RNA expression remains unclear. To address these questions, we designed a high-throughput reporter assay called enhancer x promoter (ExP) STARR-seq and applied it to examine the combinatorial compatibilities of 1,000 enhancer and 1,000 promoter sequences in human K562 cells. We identify a simple logic for enhancer-promoter compatibility – virtually all enhancers activated all promoters by similar amounts, and intrinsic enhancer and promoter activities combine multiplicatively to determine RNA output (R2=0.82). In addition, two classes of enhancers and promoters showed subtle preferential effects. Promoters of housekeeping genes contained built-in activating sequences, corresponding to motifs for factors such as GABPA and YY1, that correlated with both stronger autonomous promoter activity and enhancer activity, and weaker responsiveness to distal enhancers. Promoters of context-specific genes lacked these motifs and showed stronger responsiveness to enhancers. Together, this systematic assessment of enhancer-promoter compatibility suggests a multiplicative model tuned by enhancer and promoter class to control gene transcription in the human genome.