bluuebunny/crossref_metadata_2025 huggingface dataset:
A differential operation principle of the automatic bus transfer system pickup unit as a way of decreasing the emergency clearing time.a
Authors: Danilov Nikolay , Tsyruk Sergey , Timonin Alexandr , Sharafeddine Karam
Published: January 2022

A proper choice of the design and operation algorithm of emergency control devices like high-speed bus transfer (HSBT) is only possible proceeding from a study and analysis of steady-state and transient processes in emergency modes of operation (short-circuit faults, power supply disconnection, or phase open-circuit fault). The numerical experiments for studying such modes that were carried out, using the Matlab Simulink software package, on the mathematical models of an industrial power supply system involving synchronous motors connected to it made it possible to synthesize a new differential HSBT pickup unit featuring a high-speed response to emergency events. In doing so, special attention was paid to an analysis of transient operation modes with the aim of minimizing the probability of false actuations. The obtained study results have found practical application in the HSBT devices installed at the facilities of PJSC MOSENERGO. The experience gained from the operation of a new device jointly with high-speed circuit breakers produced by the Tavrida-Elektrik state-owned corporation has demonstrated essential advantages in comparison with the conventional HSBT designs.
Diffraction grating parameter retrieval using non-paraxial structured beams in coherent Fourier scatterometry
Authors: Soman S , Pereira S F , Gawhary O El
Published: January 2022

In recent years, a lot of works have been published that use parameter retrieval using orbital angular momentum (OAM) beams. Most make use of the OAM of different Laguerre-Gauss modes. However, those specific optical beams are paraxial beams and this limits the regime in which they can be used. In this paper, we report on the first results on retrieving the geometric parameters of a diffraction grating by analysing the corresponding complex-valued (i.e. amplitude and phase) Helmholtz Natural Modes (HNM) spectra containing both the azimuthal (i.e. n) and radial (i.e. m) indices. HNMs are a set of orthogonal, non-paraxial beams with finite energy carrying OAM. We use the coherent Fourier scatterometry (CFS) setup to calculate the field scattered from the diffraction grating. The amplitude and phase contributions of each HNM are then obtained by numerically calculating the overlap integral of the scattered field with the different modes. We show results on the sensitivity of the HNMs to several grating parameters.
The behavior of hydrothermally synthesized hematite nanorods prepared on spin coated seed layers
Authors: Talibawo Joan , Nyarige Justine S , Kyesmen Pannan I , Cyulinyana Marie C , Diale Mmantsae
Published: January 2022

Herein we report on the effect of varied spin-coated seed layer concentrations of Iron (III) chloride hexahydrate (FeCl3.6H2O) on the photoelectrochemical performance of hydrothermally synthesized hematite nanorods. The seed layers were prepared from 0.05, 0.07, 0.09, 0.11, and 0.13 M concentrations of FeCl3.6H2O. The nanorods were vertically aligned with slight inclinations over the seed layers with the two lowest molar concentrations (0.05 and 0.07 M) of FeCl3.6H2O. A further increase in seed layer concentrations transformed the nanorods as they grew over others and agglomerated into clusters. Structural analysis using x-ray diffraction (XRD) and Raman spectroscopy demonstrated uniform hematite crystalline peaks for all the samples. All samples absorbed highly in the visible region within an onset absorption edge wavelength ranging from 624 to 675 nm. Overall, the nanorods synthesized over the lowest seed layer concentration of 0.05 M of FeCl3.6H2O exhibited the highest photocurrent density of 0.077 mA cm−2 at 1.5 V versus reversible hydrogen electrode. The results obtained provide important information about the structural, optical, and photoelectrochemical properties of hematite nanorods synthesized over varied seed layer concentrations. This is a key contribution in understanding and enhancing the hematite nanorods performance for photocatalytic applications.
Photocatalytic degradation of VOCs from air stream using Mo:TiO2/GAC nanocomposites
Authors: Abedi Kamaladdin , Shahmoradi Behzad , Mohammadi Ebrahim , Wantala Kitirote , Maleki Afshin , Zandsalimi Yahya , Salimi Sonya , Kohzadi Shadi
Published: January 2022

Modification of TiO2 is one of the techniques used to enhance its photodegradation efficiency and to make it visible-light-active. In this study, Mo-doped TiO2 nanoparticles were synthesized using a fast sol-gel technique and then coated on granular activated carbon (GAC) as both substrate and adsorbent to obtain Mo:TiO2/GAC composite. The fabricated composite was characterized by many techniques such as powder XRD, SEM, EDX, FTIR, and N2 adsorption-desorption analysis. Then, the composite was applied to photodegrade volatile organic compounds (VOCs) under both UV and visible light irradiations. The characterization results showed high crystallinity and purity. Mo:TiO2/GAC composite gave a higher photodegradation efficiency compared with bare TiO2 and bare GAC. Moreover, studying operational parameters showed that the optimum condition for photodegradation efficiency of VOCs was at a flowrate of 1 L min−1, VOCs concentration of 20 ppm, and light intensity of 400 and 600 W m−2 for UV and visible light, respectively. The results suggest that Mo:TiO2/GAC is a visible-light-active composite and can be acceptably used to decompose VOCs under visible light with adequate efficiency and without the generation of harmful by-products such as O3 as compared with UV.
Ramanujan congruences for fractional partition functions
Authors: Bevilacqua Erin , Chandran Kapil , Choi Yunseo
Published: January 2022

For rational

α
\alpha

, the fractional partition functions

p
α

(
n
)

p_\alpha (n)

are given by the coefficients of the generating function

(
q
;
q

)
∞
α

(q; q)_\infty ^\alpha

. When

α
=
−
1

\alpha = -1

, one obtains the usual partition function. Congruences of the form

p
(
ℓ
n
+
c
)
≡
0

(
mod

ℓ
)

p(\ell n + c)\equiv 0 \pmod {\ell }

for a prime

ℓ
\ell

and integer

c
c

were studied by Ramanujan. Such congruences exist only for

ℓ
∈
{
5
,
7
,
11
}

\ell \in \{5, 7, 11\}

. Chan and Wang recently studied congruences for the fractional partition functions and gave several infinite families of congruences using identities of the Dedekind eta-function. Following their work, we use the theory of non-ordinary primes to find a general framework that characterizes congruences modulo any integer. This allows us to prove new congruences such as

p

57
61

(

17
2

n
−
3
)
≡
0

(
mod

17
2

)

p_\frac {57}{61}(17^2 n - 3) \equiv 0 \pmod {17^2}

.
The giants of education in geriatric medicine and gerontology
Authors: Romero-Ortuno Roman , Stuck Andreas E , Masud Tahir
Published: January 2022

In 2014, the European undergraduate curriculum in Geriatric Medicine was published to cover the minimum requirements that a medical student should achieve by the end of medical school. In 2019, the European postgraduate curriculum in Geriatric Medicine outlined the minimum recommended training requirements to become a geriatrician at specialist level in the EU. The postgraduate dimension of Geriatric Medicine education is a highly relevant topic for all, since most physicians—independently of their specialty—are inevitably involved in the care of older patients, but for most physicians, geriatrics is not part of their postgraduate generalist or specialty training. A key area for postgraduate education remains the provision of Geriatric Medicine competencies to all specialties outside geriatrics. There is also need for wider educational initiatives to improve the gerontological education of patients and the public. Bernard Isaacs famously coined the expression ‘geriatric giants’ or the four clinical I’s: Intellectual impairment, Incontinence, Immobility, and Instability. However, non-clinical giants exist. In education, we face challenges of Investment, Inspiration, Integration, and Interprofessionality; and in research, we need to attract Interest and Income, and generate Innovation and Impact. Without strengthening the links between all giants, we will not be able to achieve the ambition of age-attuned societies. A key goal for gerontological education is to enhance everyone’s understanding of the wide diversity underlying the ‘older people’ demographic label, which will ultimately promote services and societies that are more responsive and inclusive to the needs of all older adults, irrespective of their health status.
Endometriosis, Psoriasis, and Psoriatic Arthritis: A Prospective Cohort Study
Authors: Harris Holly R , Korkes Karen Moreno Nascimento , Li Tricia , Kvaskoff Marina , Cho Eunyoung , Carvalho Luiz Fernando , Qureshi Abrar A , Abrao Mauricio , Missmer Stacey A
Published: January 2022

Endometriosis, psoriasis, and psoriatic arthritis (PsA) are chronic inflammatory disorders whose etiologies remain poorly understood but may be correlated, as endometriosis has been associated with other inflammatory disorders. We investigated the bidirectional associations between laparoscopically confirmed endometriosis and physician-diagnosed psoriasis and PsA in the Nurses’ Health Study II cohort (n = 116,429, United States, 1991–2013). We confirmed 4,112 incident cases of laparoscopically confirmed endometriosis (mean age at diagnosis = 40.3 years) and 697 validated physician-diagnosed cases of psoriasis (mean age at diagnosis = 43.6 years), 110 of which presented with concomitant PsA. A history of psoriasis with concomitant PsA was associated with a 2-fold higher risk of endometriosis (hazard ratio (HR) = 2.01, 95% CI: 1.23, 3.30); however, no association was observed between psoriasis without PsA and endometriosis risk (HR = 0.93, 95% CI: 0.68, 1.26). When endometriosis was the exposure, it was not associated with a risk of subsequent psoriasis (HR = 1.28, 95% CI: 0.95, 1.72). The risk of psoriasis with PsA was notably higher; however, the sample size was small and the confidence intervals wide (HR = 1.77, 95% CI: 0.89, 3.52). Our findings suggest that psoriasis with concomitant PsA is associated with greater risk of laparoscopically confirmed endometriosis. In addition, there was a suggestive association between endometriosis diagnosis and subsequent risk of psoriasis with PsA.
Tenecteplase use in the management of acute ischemic stroke: Literature review and clinical considerations
Authors: Hailu Kirubel , Cannon Chad , Hayes Sarah
Published: January 2022

Purpose

Several research articles have been published within the last decade comparing the use of tenecteplase to alteplase in ischemic stroke management. Prior reporting on the comparative therapeutic efficacy and safety profiles of tenecteplase and alteplase is reviewed.

Tenecteplase is a variant of native tissue-type plasminogen activator, which rapidly promotes thrombolysis by catalyzing formation of the serine protease plasmin. Tenecteplase has theoretical advantages over alteplase as it has greater fibrin specificity and has a longer half-life than alteplase. This allows the administration of a single bolus over 5 to 10 seconds, as opposed to a bolus followed by a 1-hour infusion with alteplase. While currently approved by the Food and Drug Administration for the treatment of ST-segment elevation myocardial infarction, tenecteplase has also been studied in the treatment of acute ischemic stroke and has extensive data for this off-label indication. The most comprehensive trials to date evaluating the use of tenecteplase in acute ischemic stroke include the TNK-S2B, Australian TNK, ATTEST, Nor-Test, and EXTEND-IA TNK trials. Findings from these randomized controlled studies suggest that tenecteplase is at least as efficacious as alteplase in terms of neurological outcomes. The majority of these studies also reported a trend toward improved safety profiles with the use of tenecteplase.

Conclusion

Current clinical evidence shows that tenecteplase is not inferior to alteplase for the treatment of ischemic stroke and suggests that tenecteplase may have a superior safety profile. Furthermore, tenecteplase also has practical advantages in terms of its administration. This can potentially lead to a decrease in medication errors and improvement in door to thrombolytic time.
Reversing the Lens on Public Engagement with Science: Positive Benefits for Participating Scientists
Authors: Nadkarni Nalini M , Horns Joshua , Chen Jacqueline M , Morris Jeremy S , Bush Kelli , Scalice Daniella , Trivett Joslyn R , Anholt Allison
Published: January 2022

Scientists increasingly seek to respond to urgent calls for equity in science but may be unsure how to engage with underserved public groups. Prisons, jails, and detention centers are venues in which scientists may use their educational privilege to serve and empower diverse populations that are underserved by science education and underrepresented in science disciplines. We reversed the lens that traditionally focuses on the benefits of public engagement to the audience by documenting the impacts of delivering science lectures on the scientists who offered seminars to incarcerated people. The scientists who engaged in carceral settings gained professional benefits, shifted their preconceptions of incarcerated people, raised their perceived value of community engagement, and increased their interest in social justice. Some took direct actions for social change. This program could model effective engagement for other underserved groups in our society. We provide guidance to initiate such a program in other institutions.
Nonparametric causal mediation analysis for stochastic interventional (in)direct effects
Authors: Hejazi Nima S , Rudolph Kara E , Van Der Laan Mark J , Díaz Iván
Published: January 2022

Causal mediation analysis has historically been limited in two important ways: (i) a focus has traditionally been placed on binary exposures and static interventions and (ii) direct and indirect effect decompositions have been pursued that are only identifiable in the absence of intermediate confounders affected by exposure. We present a theoretical study of an (in)direct effect decomposition of the population intervention effect, defined by stochastic interventions jointly applied to the exposure and mediators. In contrast to existing proposals, our causal effects can be evaluated regardless of whether an exposure is categorical or continuous and remain well-defined even in the presence of intermediate confounders affected by exposure. Our (in)direct effects are identifiable without a restrictive assumption on cross-world counterfactual independencies, allowing for substantive conclusions drawn from them to be validated in randomized controlled trials. Beyond the novel effects introduced, we provide a careful study of nonparametric efficiency theory relevant for the construction of flexible, multiply robust estimators of our (in)direct effects, while avoiding undue restrictions induced by assuming parametric models of nuisance parameter functionals. To complement our nonparametric estimation strategy, we introduce inferential techniques for constructing confidence intervals and hypothesis tests, and discuss open-source software, the $\texttt{medshift}$$\texttt{R}$ package, implementing the proposed methodology. Application of our (in)direct effects and their nonparametric estimators is illustrated using data from a comparative effectiveness trial examining the direct and indirect effects of pharmacological therapeutics on relapse to opioid use disorder.
Leptin-reactive antibodies are distinctly correlated with body composition parameters and metabolic risk indexes in children and adolescents
Authors: Vázquez-Solórzano Rafael , Valdés-Miramontes Elia , Porchas-Quijada Mildren , Enciso-Ramírez Mayra , Contreras-Mata Guadalupe A , Martínez-Moreno Alma Gabriela , Barajas-García Lourdes , Espinoza-García Astrid Selene , Reyes-Castillo Zyanya
Published: January 2022

Studies have demonstrated the presence of low-affinity immunoglobulins (Igs) directed to leptin, a key hormone of the neuroendocrine axis that regulates appetite and metabolism, in adult healthy subjects, patients with obesity, and type 2 diabetes mellitus. In the present exploratory study, IgG leptin-reactive antibodies were analyzed for the first time in children and adolescents according to body mass index (BMI) and were correlated with biochemical profile (lipid profile, insulin, glucose, and leptin) and metabolic risk indexes [homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for β-cell function (HOMA-β), atherogenic index of plasma (AIP)]. One hundred and thirty-six participants were included (children n = 63, adolescents n = 73). An in-house enzyme-linked immunosorbent assay (ELISA) test was performed to measure IgG anti-leptin antibodies (free, total, and immune complexes). In adolescents, free and total IgG anti-leptin antibodies levels were higher in groups with overweight or obesity than in normal-weight group (P < 0.01), while in children, the total fractions were lower in groups with overweight and obesity than in normal weight (P < 0.02). Immune complexes percentage showed opposite correlations with BMI in children (r = 0.4004, P = 0.0473) and adolescents (r = −0.3983, P = 0.0133). IgG anti-leptin antibodies were also correlated with HOMA-IR in children (r = −0.4569, P = 0.0217) and adolescents (r = −0.3589, P = 0.0316), and with AIP (r = −0.3608, P = 0.0261) in adolescents. Our data suggest that the production and affinity of IgG anti-leptin antibodies can be affected by age, body composition, and metabolic conditions; additionally, in normal conditions, IgG anti-leptin antibodies may have a protective role in insulin resistance and cardiovascular events.
Interferon-gamma and perforin-positive T cells in acquired aplastic anemia: implication in therapeutic response
Authors: Sharma Vandana , Kumar Prabin , Kumar Rajiv , Chakraborty Sushmita , Namdeo Manju , Sazawal Sudha , Kanga Uma , Seth Tulika , Mitra Dipendra Kumar
Published: January 2022

Acquired aplastic anemia (aAA) is an autoimmune disease, characterized by infiltration of T lymphocytes in the bone marrow with destruction of hematopoietic stem cells by the effector cells. Interferon-gamma (IFN-γ) and perforin are important mediators of cell destruction. In this flow cytometry-based study, we have investigated the percentage of intracellular IFN-γ+ and perforin+ CD5+ T cells in peripheral blood of newly diagnosed aAA patients before and after immunosuppressive therapy (IST). Patients were categorized as per standard disease severity and response to IST. The median percentage of IFN-γ+ and perforin+ CD5+ T cells was higher in untreated patients compared to healthy controls. The percentage of these cells was also increased in untreated severe and very severe aplastic anemia when compared with non-severe aplastic anemia patients. In patients before and after IST the median percentage of T cells producing IFN-γ and perforin was elevated in non-responders as compared to partial plus complete responders. The higher percentage of IFN-γ+ and perforin+ CD5+ T cells may be useful as an early diagnostic marker for aberrant activation of immune system and predict poor response to IST in aAA patients, who will benefit from alternative therapy.
RORγt+Foxp3+ regulatory T cells in the regulation of autoimmune arthritis
Authors: Furuyama Kotona , Kondo Yuya , Shimizu Masaru , Yokosawa Masahiro , Segawa Seiji , Iizuka Akira , Tanimura Reona , Tsuboi Hiroto , Matsumoto Isao , Sumida Takayuki
Published: January 2022

RORγt+Foxp3+regulatory T (Treg) cells, known as T regulatory 17 cells (Tr17 cells), are a novel subset of Treg cells, which have the potential to regulate the development of experimental autoimmune encephalomyelitis (EAE) thorough a specific repression of T helper 17 (Th17) cell-mediated inflammation. However, the function of Tr17 cells the development of other autoimmune diseases such as autoimmune arthritis remains unclear. Collagen-induced arthritis (CIA) was found to be prolonged in Foxp3creRORγtfl/fl mice, in which Tr17 cells were deleted, compared with Foxp3wtRORγtfl/fl mice. Tr17 cells were significantly increased in ankle joints (AJ) compared with draining lymph nodes after the onset of arthritis. CC chemokine receptor 6 (CCR6) was up-regulated on Tr17 cells compared to RORγt negative Treg cells. CD25, cytotoxic T-lymphocyte antigen 4 (CTLA-4), glucocorticoid-induced TNF-receptor (GITR), and inducible T-cell co-stimulator (ICOS) expression was also up-regulated on Tr17 cells compared to RORγt negative Treg cells. IL-10-producing cells and Blimp-1+ and T-bet+ cells were increased in Tr17 cells compared to RORγt-negative Treg cells. Tr17-enriched Treg cells significantly suppressed proliferation of conventional T cells through IL-10 compared with CCR6-Treg cells. Tr17 cells increased during the clinical course of CIA and accumulated in inflamed joints. Taken together, it appears that Tr17 cells play a crucial role in the regulation of autoimmune arthritis.
Intestinal anti-tissue transglutaminase IgA deposits as a complementary method for the diagnostic evaluation of celiac disease in patients with low-grade histological lesions
Authors: Roca María , Donat Ester , Masip Etna , Ballester Verónica , Gómez Isabel , SanFelix Mercedes , Ramos David , Calvo-Lerma Joaquim , Giner-Pérez Lola , Bolonio Miguel , Polo Begoña , Ribes-Koninckx Carmen
Published: January 2022

Evaluating the usefulness of intestinal anti-transglutaminase IgA (anti-TG2 IgA) deposits detection as a complementary or decision-supporting tool in the diagnosis of celiac disease (CD) in patients with low degree of enteropathy. Small intestinal biopsies (SIB) were performed from 2008 to 2017 in patients on suspicion of CD (positive CD serology and/or symptoms) referred to our Pediatric Gastroenterology Unit. We determined anti-TG2 IgA deposits by using double immunofluorescence in all the patients in whom Marsh 0 or Marsh 1 was detected in the conventional histological study and in a random selection of patients with clearly positive serology and histological Marsh 2–3 lesion. Seventy-five pediatric patients were split into three groups according to the final diagnosis: (i) 13 children with a Marsh 0 or 1, negative CD serology and final non-CD diagnosis; none presented intestinal anti-TG2 IgA deposits; (ii) 15 potential CD cases (Marsh 0 or 1 and CD-associated antibodies), detecting anti-TG2 IgA deposits in 12; on follow-up, another biopsy performed in 11/15 showed villi atrophy in seven and a Marsh 2 lesion in two of them, patients being finally diagnosed as CD cases; and (iii) 47 children with Marsh 2–3 histological lesion and final CD diagnosis; all of them had intestinal anti-TG2 IgA deposits. Anti-TG2 deposits are a useful complementary tool for CD diagnosis in pediatric population with digestive pathologies suggestive of CD. It is especially helpful in those with low-grade lesion, in which anti-TG2 deposits are predictive of the development of more severe lesions on follow-up.
Characterization of allergic inflammation in chronic uterine cervicitis
Authors: Ma Fei , Liu Jun , Lv Xiaodan , Liu Hua-Zhen , Yang Ping-Chang , Ning Yan
Published: January 2022

Female genital tract chronic inflammation is common in clinics; the pathogenesis is not fully understood yet. House dust mite (HDM) involves the pathogenesis of many chronic diseases in human. This study aims to identify HDM-specific allergic response in the cervix of patients with cervical inflammation. Patients (n = 80) with chronic cervicitis (CC) and non-CC control (NC) subjects (n = 80) were recruited into this study. Vaginal lavage fluids (VLF) were collected from CC patients and NC subjects. Cellular components and fluid part of VLF were separated by centrifugation, and analyzed by flow cytometry and enzyme-linked immunosorbent assay. We found that a portion (52 out of 80) of CC patients responded to HDM, manifesting positive skin prick test, and HDM-specific IgE and IgG was detected in the VLF (designated CCp patients). VLF of CCp patients showed a Th2-dominant profile. HDM-specific Th2 cells were detected in VLF in CCp patients. Exposure to HDM in the culture induced proinflammatory cytokine release from CCp VLF CD4+ T cells. Exposure to CCp VLF CD4+ T cell-conditioned medium induced de novo Th2 response. Direct exposure to HDM induced allergic response in the cervix of CCp patients. In summary, a portion of CC patients respond to HDM challenge in the cervix. Exposure to HDM induces an allergy-like response in the cervix of CCp patients.
Impairment of antigen-presenting function of peripheral γδ T cells in patients with sepsis
Authors: Yang Xue-Wei , Li Hong , Feng Ting , Zhang Wei , Song Xiang-Rong , Ma Cheng-Yong , Nie Menzhen , Wang Lijie , Tan Xiaojiao , Kang Yan , Liao Xuelian
Published: January 2022

Impairment of antigen-presenting functions is a key mechanism contributing to sepsis-induced immunosuppression. Recently, γδ T cells have been demonstrated as professional antigen-presenting cells (APCs); however, their role in sepsis remains unknown. In this in vitro study, the APC function of human peripheral γδ T cells was assessed using samples collected from 42 patients with sepsis and 27 age-matched healthy controls. The APC-related markers HLA-DR, CD27, CD80, and CCR7 on fresh γδT cells were significantly higher in patients with sepsis compared with matched controls; however, they responded poorly to 4-hydroxy-3-methyl-2-butenyl pyrophosphate (HMBPP) stimulation, characterized by the deactivation of these APC markers and impaired proliferation. Furthermore, the adhesion function of γδ T cells, essential for antigen presentation, was greatly reduced in patients with sepsis; for instance, in co-cultures with green fluorescent protein-expressing Escherichia coli, HMBPP-activated γδT cells from healthy individuals adhered to E. coli efficiently, whereas no such phenomenon was observed with respect to γδT cells from patients with sepsis. In line with these results, in co-cultures with isolated CD4+ αβ T cells, HMBPP-activated γδT cells of healthy individuals promoted the efficient proliferation of CD4+ αβ T cells, whereas γδT cells from patients with sepsis did not do so. In conclusion, our findings show that the antigen-presenting function of γδT cells is severely impaired in patients with sepsis and the mechanisms behind need further study.
LncRNA MIR155HG functions as a ceRNA of miR-223-3p to promote cell pyroptosis in human degenerative NP cells
Authors: Yang Wei , Huang Xu-Dong , Zhang Tao , Zhou You-Bin , Zou Yong-Cheng , Zhang Jian
Published: January 2022

Nucleus pulposus (NP) cell pyroptosis plays a critical role in the pathogenesis of intervertebral disk degeneration (IDD). MIR155 host gene (MIR155HG) is a long non-coding RNA with pro-inflammatory activity. However, very little is known about its role in NP cell pyroptosis. This study aimed to observe the impact of MIR155HG on cell pyroptosis and to explore the underlying mechanism in human degenerative NP cells. Our results demonstrated that MIR155HG expression was significantly increased in human degenerative NP tissue samples and showed a positive correlation with Pfirrmann score. Overexpression of MIR155HG through a lentiviral vector decreased miR-223-3p levels, up-regulated NLRP3 expression and induced cell pyroptosis in human degenerative NP cells. A ceRNA action mode was identified among MIR155HG, miR-223-3p, and NLRP3. The stimulatory effect of MIR155HG on human degenerative NP cell pyroptosis was significantly reversed by pretreatment with miR-223-3p mimic or NLRP3 siRNA. In summary, these data suggest that MIR155HG sponges miR-223-3p to promote NLRP3 expression, leading to induction of cell pyroptosis in human degenerative NP cells. Targeting MIR155HG could be a novel and promising strategy to slow down the progression of IDD.
Droplet digital PCR for identifying copy number variations in patients with primary immunodeficiency disorders
Authors: Woon See-Tarn , Mayes Julia , Quach Alexander , Longhurst Hilary , Ferrante Antonio , Ameratunga Rohan
Published: January 2022

Primary immunodeficiency disorders comprise a rare group of mostly monogenic disorders caused by inborn errors of immunity. The majority can be identified by either Sanger sequencing or next generation sequencing. Some disorders result from large insertions or deletions leading to copy number variations (CNVs). Sanger sequencing may not identify these mutations. Here we present droplet digital PCR as an alternative cost-effective diagnostic method to identify CNV in these genes. The data from patients with large deletions of NFKB1, SERPING1, and SH2D1A are presented.
Common brain cortical abnormality in smoking behavior and bipolar disorder: discriminant analysis using cortical thickness and surface area
Authors: Ohi Kazutaka , Takai Kentaro , Kuramitsu Ayumi , Sugiyama Shunsuke , Shioiri Toshiki
Published: January 2022

Cigarette smoking is highly prevalent among patients with bipolar disorder (BD). Structural brain abnormalities related to smoking behavior and BD risk are indicated by magnetic resonance imaging (MRI) studies. However, cortical alterations common to smoking behavior and BD remain unclear. Our purpose was to identify common cortical alterations between smoking behavior and BD. 3T MRI-based indices of cortical thickness and surface area using FreeSurfer were acquired from 166 healthy control (HC) nonsmokers, 39 HC smokers, 33 BD nonsmokers, and 18 BD smokers. A stepwise discriminant-function analysis (DFA) with cortical structures as predictors was performed to classify BD patients into nonsmokers and smokers. Next, DFAs with the selected structures as predictors were performed to discriminate smoking status or diagnostic status. Differences in the selected features among the four groups were examined. The first DFA showed that six brain features discriminated between nonsmokers and smokers among BD patients. The six brain features related to BD smoking status also discriminated between HCs and BD patients and HC nonsmokers and BD smokers. Among the six features, left insular thickness showed a negative additive effect of smoking status and BD diagnosis. Our findings suggest the common neurobiological involvement of insular thickness in smoking behavior and BDrisk.
High-definition transcranial direct current stimulation enhances network segregation during spatial navigation in mild cognitive impairment
Authors: Iordan Alexandru D , Ryan Shannon , Tyszkowski Troy , Peltier Scott J , Rahman-Filipiak Annalise , Hampstead Benjamin M
Published: January 2022

Spatial navigation is essential for everyday life and relies on complex network-level interactions. Recent evidence suggests that transcranial direct current stimulation (tDCS) can influence the activity of large-scale functional brain networks. We characterized brain-wide changes in functional network segregation (i.e. the balance of within vs. between-network connectivity strength) induced by high-definition (HD) tDCS in older adults with mild cognitive impairment (MCI) during virtual spatial navigation. Twenty patients with MCI and 22 cognitively intact older adults (healthy controls—HC) underwent functional magnetic resonance imaging following two counterbalanced HD-tDCS sessions (one active, one sham) that targeted the right parietal cortex (center anode at P2) and delivered 2 mA for 20 min. Compared to HC, MCI patients showed lower brain-wide network segregation following sham HD-tDCS. However, following active HD-tDCS, MCI patients’ network segregation increased to levels similar to those in HC, suggesting functional normalization. Follow-up analyses indicated that the increase in network segregation for MCI patients was driven by HD-tDCS effects on the “high-level”/association brain networks, in particular the dorsal-attention and default-mode networks. HD-tDCS over the right parietal cortex may normalize the segregation/integration balance of association networks during spatial navigation in MCI patients, highlighting its potential to restore brain activity in Alzheimer’s disease.
Detecting, preventing and treating non-adherence to immunosuppression after kidney transplantation
Authors: Gandolfini Ilaria , Palmisano Alessandra , Fiaccadori Enrico , Cravedi Paolo , Maggiore Umberto
Published: January 2022

Medication non-adherence (MNA) is a major issue in kidney transplantation and it is associated with increased risk of rejection, allograft loss, patients’ death and higher healthcare costs. Despite its crucial importance, it is still unclear what are the best strategies to diagnose, prevent and treat MNA. MNA can be intentional (deliberate refusal to take the medication as prescribed) or unintentional (non-deliberate missing the prescribed medication). Its diagnosis may rely on direct methods, aiming at measuring drug ingestions, or indirect methods that analyse the habits of patients to adhere to correct drug dose (taking adherence) and interval (time adherence). Identifying individual risk factors for MNA may provide the basis for a personalized approach to the treatment of MNA. Randomized control trials performed so far have tested a combination of strategies, such as enhancing medication adherence through the commitment of healthcare personnel involved in drug distribution, the use of electronic reminders, therapy simplification or various multidisciplinary approaches to maximize the correction of individual risk factors. Although most of these approaches reduced MNA in the short-term, the long-term effects on MNA and, more importantly, on clinical outcomes remain unclear. In this review, we provide a critical appraisal of traditional and newer methods for detecting, preventing and treating non-adherence to immunosuppression after kidney transplantation from the perspective of the practising physician.
phytochemdb: a platform for virtual screening and computer-aided drug designing
Authors: Mahmud Shafi , Paul Gobindo Kumar , Biswas Suvro , Kazi Taheruzzaman , Mahbub Shafquat , Mita Mohasana Akter , Afrose Shamima , Islam Ariful , Ahaduzzaman Sheikh , Hasan Md. Robiul , Shimu Mst. Sharmin Sultana , Promi Maria Meha , Shehab Mobasshir Noor , Rahman Ekhtiar , Sujon Khaled Mahmud , Alom Md. Wasim , Modak Anik , Zaman Shahriar , Uddin Md. Salah , Emran Talha Bin , Islam Md. Sayeedul , Saleh Md. Abu
Published: January 2022

The phytochemicals of medicinal plants are regarded as a rich source of diverse chemical spaces that have been used as supplements and alternative medicines in the millennium. Even in this era of combinatorial chemical drugs, phytomedicines account for a large share of the statistics of newly approved drugs. In the field of computational aided and rational drug design, there is an urgent need to develop and build a useful phytochemical database management system with a user-friendly interface that allows proper data storage, retrieval and management. We showed ‘phytochemdb’, a manually managed database that compiles 525 plants and their corresponding 8093 phytochemicals, aiming to incorporate the activities of phytochemicals from medicinal plants. The database collects molecular formula, three-dimensional/two-dimensional structure, canonical SMILES, molecular weight, no. of heavy atoms, no. of aromatic heavy atoms, fraction Csp3, no. of rotatable bonds, no. of H-bond acceptors, no. of H-bond donors, molar refractivity, topological polar surface area, gastrointestinal absorption, Blood–Brain Barrier (BBB) permeant, P-gp substrate, CYP1A2 inhibitor, CYP2C19 inhibitor, CYP2C9 inhibitor, CYP2D6 inhibitor, CYP3A4 inhibitor, Log Kp, Ghose, Veber, Egan, Muegge, bioavailability scores, pan-assay interference compounds, Brenk, Leadlikeness, synthetic accessibility, iLOGP and Lipinski rule of five with the number of violations for each compound. It provides open contribution functions for the researchers who screen phytochemicals in the laboratory and have released their data. ‘phytochemdb’ is a comprehensive database that gathers most of the information about medicinal plants in one platform, which is considered to be very beneficial to the work of researchers on medicinal plants. ‘phytochemdb’ is available for free at https://phytochemdb.com/.
Tricuspid regurgitation: recent advances in understanding pathophysiology, severity grading and outcome
Authors: Hahn Rebecca T , Badano Luigi P , Bartko Philipp E , Muraru Denisa , Maisano Francesco , Zamorano Jose L , Donal Erwan
Published: January 2022

Heightened interest in tricuspid regurgitation (TR) stems from the consistent association of mortality with greater severity of TR, and a low use of surgical solutions in the setting of high in-hospital mortality attributed to the late presentation of the disease. The delay in intervention is likely related to a limited understanding of the valvular/ventricular anatomy and disease pathophysiology, along with an underestimation of TR severity by standard imaging modalities. With the rapid development of transcatheter solutions which have shown early safety and efficacy, there is a growing need to understand and accurately diagnose the valvular disease process in order to determine appropriate management solutions. The current review will describe both normal and pathologic tricuspid valvular anatomy, the classification of these anatomic substrates of TR, the strengths and limitations of the current guidelines-recommended multi-parametric echocardiographic approach and the role of multi-modality imaging, as well as the role of transcatheter device therapy in the management of the disease.
The Brides of Boko Haram: Economic Shocks, Marriage Practices, and Insurgency in Nigeria
Authors: Rexer Jonah M
Published: January 2022

Marriage markets in rural Nigeria are characterised by bride price and polygamy. These customs may diminish marriage prospects for young men, causing them to join militant groups. Using an instrumental variables strategy, I find that marriage inequality increases civil conflict in the Boko Haram insurgency. To generate exogenous shocks to the marriage market, I exploit the fact that young women delay marriage in response to favourable pre-marital economic conditions, which increases marriage inequality primarily in polygamous villages. The same shocks that increase marriage inequality and extremist violence also lead women to marry fewer and richer husbands, generate higher average marriage expenditures, and increase insurgent abductions. The results shed light on the marriage market as an important driver of violent extremism.
What kind of EU fiscal capacity? Evidence from a randomized survey experiment in five European countries in times of corona
Authors: Beetsma Roel , Burgoon Brian , Nicoli Francesco , de Ruijter Anniek , Vandenbroucke Frank
Published: January 2022

Based on a conjoint survey experiment, we explore the support among European citizens for a European Union (EU) budgetary assistance instrument to combat adverse temporary or permanent economic shocks hitting Member States. Suitably designed, there is substantial support for such an EU instrument generally and across the sample countries. Support is broader when budgetary support is conditional on debt reduction in good times and on monies being spent in specific policy areas, in particular healthcare and education. Support also increases when there is a role for the European Commission in terms of monitoring and providing guidance. However, there is little support for policy packages that terminate a programme and impose fines in the case of non-compliance. Further, there is broad acceptance of programmes that entail long-run redistribution towards poorer countries. Financing the assistance through a progressive tax increase is more popular than through a flat tax increase. In general, there is substantial scope for constructing assistance packages that command majority support in all sample countries, particularly if programmes have spending conditionality and progressive tax financing.
Silent brain infarcts impact on cognitive function in atrial fibrillation
Authors: Kühne Michael , Krisai Philipp , Coslovsky Michael , Rodondi Nicolas , Müller Andreas , Beer Jürg H , Ammann Peter , Auricchio Angelo , Moschovitis Giorgio , Hayoz Daniel , Kobza Richard , Shah Dipen , Stephan Frank Peter , Schläpfer Jürg , Di Valentino Marcello , Aeschbacher Stefanie , Ehret Georg , Eken Ceylan , Monsch Andreas , Roten Laurent , Schwenkglenks Matthias , Springer Anne , Sticherling Christian , Reichlin Tobias , Zuern Christine S , Meyre Pascal B , Blum Steffen , Sinnecker Tim , Würfel Jens , Bonati Leo H. , Conen David , Osswald Stefan ,   for the Swiss-AF Investigators
Published: January 2022

Aims

We aimed to investigate the association of clinically overt and silent brain lesions with cognitive function in atrial fibrillation (AF) patients.

Methods and results

We enrolled 1227 AF patients in a prospective, multicentre cohort study (Swiss-AF). Patients underwent standardized brain magnetic resonance imaging (MRI) at baseline and after 2 years. We quantified new small non-cortical infarcts (SNCIs) and large non-cortical or cortical infarcts (LNCCIs), white matter lesions (WML), and microbleeds (Mb). Clinically, silent infarcts were defined as new SNCI/LNCCI on follow-up MRI in patients without a clinical stroke or transient ischaemic attack (TIA) during follow-up. Cognition was assessed using validated tests. The mean age was 71 years, 26.1% were females, and 89.9% were anticoagulated. Twenty-eight patients (2.3%) experienced a stroke/TIA during 2 years of follow-up. Of the 68 (5.5%) patients with ≥1 SNCI/LNCCI, 60 (88.2%) were anticoagulated at baseline and 58 (85.3%) had a silent infarct. Patients with brain infarcts had a larger decline in cognition [median (interquartile range)] changes in Cognitive Construct score [−0.12 (−0.22; −0.07)] than patients without new brain infarcts [0.07 (−0.09; 0.25)]. New WML or Mb were not associated with cognitive decline.

Conclusion

In a contemporary cohort of AF patients, 5.5% had a new brain infarct on MRI after 2 years. The majority of these infarcts was clinically silent and occurred in anticoagulated patients. Clinically, overt and silent brain infarcts had a similar impact on cognitive decline.

Clinical Trial Registration

ClinicalTrials.gov Identifier: NCT02105844, https://clinicaltrials.gov/ct2/show/NCT02105844
Predicting daily COVID-19 case rates from SARS-CoV-2 RNA concentrations across a diversity of wastewater catchments
Authors: Zulli Alessandro , Pan Annabelle , Bart Stephen M , Crawford Forrest W , Kaplan Edward H , Cartter Matthew , Ko Albert I , Sanchez Marcela , Brown Cade , Cozens Duncan , Brackney Doug E , Peccia Jordan
Published: January 2022

We assessed the relationship between municipality COVID-19 case rates and SARS-CoV-2 concentrations in the primary sludge of corresponding wastewater treatment facilities. Over 1700 daily primary sludge samples were collected from six wastewater treatment facilities with catchments serving 18 cities and towns in the State of Connecticut, USA. Samples were analyzed for SARS-CoV-2 RNA concentrations during a 10 month time period that overlapped with October 2020 and winter/spring 2021 COVID-19 outbreaks in each municipality. We fit lagged regression models to estimate reported case rates in the six municipalities from SARS-CoV-2 RNA concentrations collected daily from corresponding wastewater treatment facilities. Results demonstrate the ability of SARS-CoV-2 RNA concentrations in primary sludge to estimate COVID-19 reported case rates across treatment facilities and wastewater catchments, with coverage probabilities ranging from 0.94 to 0.96. Lags of 0 to 1 days resulted in the greatest predictive power for the model. Leave-one-out cross validation suggests that the model can be broadly applied to wastewater catchments that range in more than one order of magnitude in population served. The close relationship between case rates and SARS-CoV-2 concentrations demonstrates the utility of using primary sludge samples for monitoring COVID-19 outbreak dynamics. Estimating case rates from wastewater data can be useful in locations with limited testing availability, testing disparities, or delays in individual COVID-19 testing programs.
The diversity of heme sensor systems – heme-responsive transcriptional regulation mediated by transient heme protein interactions
Authors: Krüger Aileen , Keppel Marc , Sharma Vikas , Frunzke Julia
Published: January 2022

Heme is a versatile molecule that is vital for nearly all cellular life by serving as prosthetic group for various enzymes or as nutritional iron source for diverse microbial species. However, elevated levels of heme is toxic to cells. The complexity of this stimulus has shaped the evolution of diverse heme sensor systems, which are involved in heme-dependent transcriptional regulation in eukaryotes and prokaryotes. The functions of these systems are manifold—ranging from the specific control of heme detoxification or uptake systems to the global integration of heme and iron homeostasis. This review focuses on heme sensor systems, regulating heme homeostasis by transient heme protein interaction. We provide an overview of known heme-binding motifs in prokaryotic and eukaryotic transcription factors. Besides the central ligands, the surrounding amino acid environment was shown to play a pivotal role in heme binding. The diversity of heme-regulatory systems, therefore, illustrates that prediction based on pure sequence information is hardly possible and requires careful experimental validation. Comprehensive understanding of heme-regulated processes is not only important for our understanding of cellular physiology, but also provides a basis for the development of novel antibacterial drugs and metabolic engineering strategies.
Haplotype-based inference of the distribution of fitness effects
Authors: Ortega-Del Vecchyo Diego , Lohmueller Kirk E , Novembre John
Published: January 2022

Recent genome sequencing studies with large sample sizes in humans have discovered a vast quantity of low-frequency variants, providing an important source of information to analyze how selection is acting on human genetic variation. In order to estimate the strength of natural selection acting on low-frequency variants, we have developed a likelihood-based method that uses the lengths of pairwise identity-by-state between haplotypes carrying low-frequency variants. We show that in some nonequilibrium populations (such as those that have had recent population expansions) it is possible to distinguish between positive or negative selection acting on a set of variants. With our new framework, one can infer a fixed selection intensity acting on a set of variants at a particular frequency, or a distribution of selection coefficients for standing variants and new mutations. We show an application of our method to the UK10K phased haplotype dataset of individuals.