bluuebunny/crossref_metadata_2025 huggingface dataset:
FIGURE 6 from D-2-HG Inhibits IDH1mut Glioma Growth via FTO Inhibition and Resultant m6A Hypermethylation
Authors: Pianka Sean T. , Li Tie , Prins Terry J. , Eldred Blaine S.C. , Kevan Bryan M. , Liang Haowen , Zapanta Rinonos Serendipity , Kornblum Harley I. , Nathanson David A. , Pellegrini Matteo , Liau Linda M. , Nghiemphu Phioanh Leia , Cloughesy Timothy F. , Lai Albert
Published: March 2024

ATF5 is a downstream mediator of the IDH1mut → D-2-HG ⊣ FTO axis leading to gliomasphere growth reduction. A, m6A called peaks of ATF5 mRNA from MeRIP-seq RADAR data aligned to the genome (GRCh38). Inset graph shows m6A enrichment in IDH1mut (salmon) versus IDH1wt (teal) glioma samples for a select coding (exon) region, indicated by the dashed box. IP indicates immunoprecipitated mRNA fraction containing m6A-enriched RNA. INPUT mRNA fraction indicates total mRNA. B, Increased m6A-enriched ATF5 mRNA content in patient IDH1mut gliomas (n = 13) detected by m6A immunoprecipitation qRT-PCR, compared with IDH1wt gliomas (n = 10) (P ≤ 0.05). C, Decreased ATF5 mRNA m6A content detected by ATF5 qRT-PCR in the same IDH1mut gliomas (P ≤ 0.008). D, Pooled data from IDHwt gliomaspheres (HK217 and HK250) showing induction of ATF5 mRNA m6A enrichment following IDH1mut forced expression and its subsequent attenuation following treatment with IDH1mut inhibitor AG881 (1 µmol/L). E, Pooled data from IDHwt gliomaspheres (HK217 and HK250) showing a reduction of ATF5 mRNA expression following IDH1mut forced expression and ATF5 mRNA expression rescue following AG881 (1 µmol/L) treatment. F, ATF5 protein levels are decreased in gliomaspheres following IDH1mut forced expression and are rescued following treatment with IDH1mut inhibitor AG881 (1 µmol/L). ATF5 protein expression was determined relative to α-tubulin protein loading controls. G, Octyl-D-2-HG (0.5 mmol/L) or FTO inhibitor FB23-2 (3 µmol/L) treatment reduced ATF5 protein expression in IDH1wt gliomaspheres. H,IDH1wt gliomaspheres (HK250) transfected with piLenti-siRNA-GFP, expressing shRNA for either NSC or two regions (A, B) of ATF5, show reduced ATF5 expression via Western blot analysis (left) and reduced sphere growth (right). I, Schematic representation of the IDH1mut ⊣ FTO axis resulting in m6A enrichment and subsequent degradation of ATF5 mRNA transcripts leading to increased apoptosis. (P ≤ 0.005). *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; and ****, P ≤ 0.0001 compared with relevant controls. Unless otherwise stated, P values indicate unpaired Student t test comparisons with the control, or between two groups as indicated by the horizontal line.
FIGURE 3 from D-2-HG Inhibits IDH1mut Glioma Growth via FTO Inhibition and Resultant m6A Hypermethylation
Authors: Pianka Sean T. , Li Tie , Prins Terry J. , Eldred Blaine S.C. , Kevan Bryan M. , Liang Haowen , Zapanta Rinonos Serendipity , Kornblum Harley I. , Nathanson David A. , Pellegrini Matteo , Liau Linda M. , Nghiemphu Phioanh Leia , Cloughesy Timothy F. , Lai Albert
Published: March 2024

Role of m6A demethylases FTO and ALKBH5 in mediating m6A hypermethylation and growth inhibition. A, Western blot images of FTO, ALKBH5 and α-tubulin protein content following DARTS assay in U87 cells. B, Normalized densities of Western blots in A, showing increased protected protein density in FTO lysates treated with D-2-HG over ALKBH5. The effect of FTO versus ALKBH5 lysates on protected protein density was evaluated via ANOVA [F(1,30) = 27.2, P ≤ 0.0001; asterisks indicate post hoc Newman–Keuls comparison within treatment of D-2HG, or between groups as indicated by the horizontal bars]. The densities of FTO and ALKBH5 DARTS products were normalized with parallel FTO and ALKBH5 Western blot densities of mock DARTS products (no protease added). C, Western blot analysis showing downregulation of FTO and ALKBH5 following shRNA knockdown in U87. D, Greater effect of FTO than ALKBH5 knockdown (shRNA) on increasing m6A content in U87. Treatment with shFTO and shALKBH5 was similar to shFTO only treatment. E, MTT assays demonstrating that shRNA treatment (shFTO, or shFTO and shALKBH5) reduces the viability of U87 cell lines [ANOVA, F(3,8) = 39.1, P ≤ 0.0001]. Treatment effect was heterogenous regarding FTO and ALKBH5, with shFTO demonstrating an effect on cell viability and shALKBH5 having no effect in comparison with a scrambled sequence (NSC; post hoc Newman–Keuls comparisons, indicated by the asterisks and brackets). Western blots showing downregulation of FTO and ALKBH5 following shRNA knockdown in HK217 (F) and HK250 (G) gliomaspheres. FTO knockdown (shRNA) has a greater effect on m6A content increases than ALKBH5 in HK217 (H) and HK250 (I) gliomaspheres. FTO knockdown (shRNA) is more effective at reducing sphere growth than ALKBH5 in HK217 (J) and HK250 (K) gliomaspheres. Western blots showing successful overexpression of FTOwt and inactivated FTOmut control in HK217 (L) and HK250 (M) gliomaspheres. FTOwt overexpression increases gliomasphere growth in comparison with inactivated FTOmut control in HK217 (N, P ≤ 0.0006) and HK250 (O, P ≤ 0.002) gliomaspheres. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; and ****, P ≤ 0.0001 compared with relevant controls. Unless otherwise stated, P-values indicate unpaired Student t test comparisons with the control, or between two groups as indicated by the horizontal line.
Uma breve história do eternalismo
Authors: Jacobs Ken
Published: March 2024

Minha esposa Flo e eu então começamos a esfregar perspectivas próximas junto com um sistema de dupla projeção que chamei de O Sistema Nervoso, que produzia loucas visões, oscilando entre o reconhecível e o inimaginável. E foi aqui que surgiu o Eternalismo. (...) Uma alternância constante e a repetição de fotogramas próximos em sequência, mais um intervalo de preto entre as repetições, não apenas faz a profundidade aparecer como também cria movimento, um movimento 3D que permanece unidirecional, não retornando e então seguindo mais uma vez; um movimento capturado, indo para lugar nenhum, o Eternalismo.
Time Found Footage: material de arquivo Proustiano editado reflexivamente.
Authors: Nader Carlos
Published: March 2024

Como toda obra que primeiro se debruça sobre temas essenciais da condição humana e que depois revela-se ela mesma também essencial para a condição humana, À La Recherche du Temps Perdu de Marcel Proust é milionária em paradoxos. Um deles, absolutamente periférico para a humanidade mas central para mim, é o fato de que por um lado a Recherche traz a receita mais extensa e exata do cinema que eu escolhi fazer e que, por outro, Proust sequer achava que o cinema fosse uma arte digna do nome.
Standard Gauge
Authors: Fisher Morgan
Published: March 2024

Uma moldura de molduras, um pedaço de pedaços, um comprimento de comprimentos. Calibre padrão abaixo do padrão; mais estreito, sim, mas mais longo. Uma ECU que é um ELS. Disjecta membra; antologia de Hollywood. Uma espécie de autobiografia de seu criador, uma espécie de história da instituição de cujos fragmentos é composta, a indústria do cinema comercial. Uma interrogação mútua entre 35mm e 16mm, a bitola de Hollywood, e a bitola do amador e independente.
Examination of the Effect of the Real-Life Meaning of the Stimulus on the Self-Motion Illusion
Authors: Jiang Moyou , Guo Xuanru , Seno Takeharu , Remijn Gerard B. , Nakamura Shinji
Published: March 2024

Vection refers to the illusory self-motion perception mainly induced by the motion of a visual stimulus. This phenomenon concerns presence and immersion in the illusion of self-motion, especially in virtual reality. In the present study, we investigated how the real-life meaning of stimuli contributes to vection by using animations of objects that can move by themselves. In two psychophysical experiments, we first employed animated cars presented with or without wheel rotation as the visual inducer, using various motion directions and postures; then we added the road scenery, which was either moving (in the same or opposite direction to the cars) or still, as a contextual background in the visual stimulus. The results of Experiment 1 showed that in conditions with forward- and backward-moving cars, vection was stronger than in conditions with upward-moving and inverted cars. The results of Experiment 2 showed that vection was weakest in the still road scenery condition and that the cars’ wheel rotation could facilitate vection. This suggests that the more natural the stimulus meanings, the stronger the vection. It is a feasible and effective application prospect to enhance the vection experience by changing the naturalness of the stimulus to further increase the sense of presence and immersion. Therefore, the perceived naturalness and the assumed immobility of the visual inducer are two important cognitive factors in visual self-motion perception and presence in the virtual world.
‘De voix femmenine’: Self, Voice and Emotive Display in Jean d’Arras’s Mélusine
Authors: R. de la Torre Meritxell
Published: March 2024

The 14th century French romance Mélusine ou la Noble Histoire de Lusignan focuses on the peculiar founding mother of the house of Lusignan, who, due to a curse imposed by her fairy mother, is forced to transform in secrecy into a half-serpent, half-human figure every Saturday. The romance depicts her life after the curse and her ultimate exile after her husband discovers her in her hybrid form. As the lady flies away fully transformed into a giant serpent, however, marks of her enduring selfhood prevail: first, in a mark embedded in a windowsill in the shape of a foot and later, as a voiced emotional complaint, described as the voice of a woman. The serpent’s emotive display confirms the existence of a stable, yet malleable core selfhood in the character that prevails through her embodied changes. The goal is to establish emotive display as an effective tool to access narrated selfhood in the romance.
Management of a Complex Fistula Involving Abdominal Wall, Small Bowel, Colon, and Bladder
Authors: Gillani Mishal , Rosen Seth A.
Published: March 2024

Successful surgical management of a chronic complex abdominal fistula requires thoughtful pre-operative evaluation and planning and often benefits from a multi-disciplinary approach. Initially, attention is focused on controlling sepsis and ensuring adequate hydration and electrolyte replacement. Next, efforts to optimize nutrition and engage the patient in prehabilitation are prioritized. Simultaneously, imaging is used to gain detailed assessment of anatomy. We present a challenging case involving a Jackson-Pratt (JP) drain from prior surgery causing a complex intra-abdominal fistula. The JP drain traversed multiple small bowel loops and the sigmoid colon before terminating in the bladder. Management required multi-disciplinary coordination involving colorectal surgery and urology. The patient’s definitive surgery included anterior resection, colostomy takedown, right colectomy, three small bowel resections, and bladder repair. The use of JP drains after abdominal surgery is not without risk. Clinicians should have standardized indications for placement of JP drains and consistent protocols regarding timing of removal.
Complete and Accurate? The Role of Profit Orientation in the Production of Public Health Data
Authors: Hoffmann Elina S. , Karplus Valerie J. , Fuchs Erica R. H.
Published: March 2024

Public officials rely on performance data that are self-reported by organizations to evaluate progress on a wide range of prosocial outcomes. Policies that require public disclosure of performance in health care are thought to enable patients to select high-quality providers, which in turn may spur quality improvements as providers seek to protect their reputation or increase economic returns. Drawing on institutional theory that examines how conflicting institutional pressures influence organizational decisions, we theorize how profit orientation may mediate the response of health care providers to disclosure mandates in a public health crisis. We focus on measures of data quality—completeness and accuracy—in self-reported data on COVID-19 status and outcomes generated by thousands of long-term care facilities. Using pooled regressions and a difference-in-differences style design, we find that overall, for-profit and not-for-profit facilities report similarly complete data but that for-profit facilities report less accurate data than their not-for-profit counterparts. Our results suggest that it may be important to incentivize each dimension of data quality separately to address differential institutional pressures that affect reporting practices.
ACO Clinicians Have Higher Medicare Part B Medical Services Payments Than MIPS Clinicians Under the Quality Payment Program
Authors: Shrestha Mina , Sharma Hari , Mueller Keith J.
Published: March 2024

The Quality Payment Program (QPP) is a Medicare value-based payment program with 2 tracks: -Advanced Alternative Payment Models (A-APMs), including two-sided risk Accountable Care Organizations (ACOs), and Merit-based Incentive Payment System (MIPS). In 2020, A-APM eligible ACO clinicians received an additional 5% positive, and MIPS clinicians received up to 5% negative or 2% positive performance-based adjustments to their Medicare Part B medical services payments. It is unclear whether the different payment adjustments have differential impacts on total medical services payments for ACO and MIPS participants. We compare Medicare Part B medical services payments received by primary care clinicians participating in ACO and MIPS programs using Medicare Provider Utilization and Payment Public Use Files from 2014 to 2018 using difference-in-differences regressions. We have 254 395 observations from 50 879 unique clinicians (ACO = 37.86%; MIPS = 62.14%). Regression results suggest that ACO clinicians have significantly higher Medicare Part B medical services payments ($1003.88; 95% CI: [579.08, 1428.69]) when compared to MIPS clinicians. Our findings suggest that ACO clinicians had a greater increase in medical services payments when compared to MIPS clinicians following QPP participation. Increased payments for Medicare Part B medical services among ACO clinicians may be driven partly by higher payment adjustment rates for ACO clinicians for Part B medical services. However, increased Part B medical services payments could also reflect clinicians switching to increased outpatient services to prevent potentially costly inpatient services. Policymakers should examine both aspects when evaluating QPP effectiveness.
Disaggregating the liberal market economies: Institutions and HRM
Authors: Brewster Chris , Brookes Michael , Wood Geoffrey
Published: March 2024

It has been argued that the different ways human resource management is conducted in different countries can be at least partly explained by theories of comparative capitalisms. Earlier work has highlighted much diversity between coordinated market economies, but the liberal markets are commonly assumed to represent a more coherent category. This article scrutinizes the latter assumption more closely by examining differences between the liberal market economies in their approaches to HRM. The authors find that the USA displays greater centralization in human resource management practices, higher turnover rates and less delegation to employees, than in the UK and Australia; this being associated with differences in institutional realities. The study highlights how, under a broad institutional archetype, specific systemic features may exert strong effects on specific HRM practices and challenges assumptions of close institutional coupling in the most advanced economies.
Let Us Sing to God: The Value of Asian Congregational Songs for Liturgy and Mission
Authors: Lim Swee Hong
Published: March 2024

Presently, many Asian churches continue to depend on translated Western congregational songs in their public Christian worship. This essay investigates the historical development of localized Asian Congregational Songs describing how this development in worship music-making was influenced by the reorientation in missiological thinking in the early twentieth century that bore fruit in the 1960s as churches in the Global South became autonomous. Thereafter demonstrate how this genre of congregational songs, guided by theological hermeneutical principles, can offer a viable pathway for contextually determined Asian Christian identity in the twenty-first century through the postcolonial hybrid congregational song form—a genre that holds in balance the original cultural identity of the song and the adaptability of the genre to navigate cultural boundaries.
Long-term Outcomes of Primary Hip Arthroscopy: Multicenter Analysis at Minimum 10-Year Follow-up With Attention to Labral and Capsular Management
Authors: Boos Alexander M. , Wang Allen S. , Lamba Abhinav , Okoroha Kelechi R. , Ortiguera Cedric J. , Levy Bruce A. , Krych Aaron J. , Hevesi Mario
Published: March 2024

Background:

Hip arthroscopy is rapidly advancing, with positive published outcomes at short- and midterm follow-up; however, available long-term data remain limited.

Purpose:

To evaluate outcomes of primary hip arthroscopy at a minimum 10-year follow-up at 2 academic centers by describing patient-reported outcomes and determining reoperation and total hip arthroplasty (THA) rates.

Study Design:

Case series; Level of evidence, 4.

Methods:

Patients with primary hip arthroscopy performed between January 1988 and April 2013 at 2 academic centers were evaluated for postoperative patient-reported outcomes—including the visual analog scale, Tegner Activity Scale score, Hip Outcome Score Activities of Daily Living and Sport Specific subscales, modified Harris Hip Score, Nonarthritic Hip Score, 12-item International Hip Outcome Tool, surgery satisfaction, and reoperations.

Results:

A total of 294 patients undergoing primary hip arthroscopy (age, 40 ± 14 years; 66% women; body mass index, 27 ± 6) were followed for 12 ± 3 years (range, 10-24 years) postoperatively. Labral debridement and repair were performed in 41% and 59% of patients, respectively. Of all patients who underwent interportal capsulotomy, 2% were extended to a T-capsulotomy, and 11% underwent capsular repair. At final follow-up, patients reported a mean visual analog scale at rest of 2 ± 2 and with use of 3 ± 3, a 12-item International Hip Outcome Tool of 68 ± 27, a Nonarthritic Hip Score of 81 ± 18, a modified Harris Hip Score of 79 ± 17, and a Hip Outcome Score Activities of Daily Living of 82 ± 19 and Sport Specific subscale of 74 ± 25. The mean surgical satisfaction was 8.4 ± 2.4 on a 10-point scale, with 10 representing the highest level of satisfaction. In total, 96 hips (33%) underwent reoperation—including 65 hips (22%) converting to THA. THA risk factors included older age, higher body mass index, lower lateral center-edge angle, larger alpha angle, higher preoperative Tönnis grade, as well as labral debridement and capsular nonrepair ( P≤ .039). Patients undergoing combined labral and capsular repair demonstrated a THA conversion rate of 3% compared with 31% for patients undergoing combined labral debridement and capsular nonrepair ( P = .006). Labral repair trended toward increased 10-year THA-free survival (84% vs 77%; P = .085), while capsular repair demonstrated significantly increased 10-year THA-free survival (97% vs 79%; P = .033).

Conclusion:

At a minimum 10-year follow-up, patients undergoing primary hip arthroscopy demonstrated high satisfaction and acceptable outcome scores. In total, 33% of patients underwent reoperation—including 22% who underwent THA. Conversion to THA was associated with patient factors including older age, higher Tönnis grade, and potentially modifiable surgical factors such as labral debridement and capsular nonrepair.
Adaptive coordinated control strategy for improving shift quality under different operating conditions
Authors: Shang Xianhe , Zhang Fujun , Zhang Zhenyu , Cui Tao
Published: March 2024

In order to improve the shift quality of vehicles under different operating conditions (such as road resistance coefficient and throttle opening), this paper proposes an adaptive coordinated control strategy. This strategy utilizes a Forgetting Factor Recursive Least Squares (FFRLS) to achieve online identification of the road resistance coefficient. Based on the changes in throttle pedal opening and road resistance coefficient during the vehicle’s shifting process, the strategy adaptively adjusts the coordinated control parameter (fuel cut-off time) to achieve optimal control of vehicle shifting under different operating conditions. To evaluate the shift quality, shift jerk, friction work, torque peak, and shift time are used as performance indicators. Based on a constructed simulation model of the powertrain system, the influence of different operating conditions on the performance indicators is analyzed, and the effect of coordinated control parameters on improving shift quality under different operating conditions is compared. Corresponding fuzzy rules are then established to achieve adaptive adjustment of the coordinated control parameters through fuzzy control, ensuring effective improvement of shift quality for vehicles under different operating conditions.
A comparative study of flake graphite iron and compacted graphite iron in austempered condition for directional control valves
Authors: Thilak G. , Chandramohan P. , Saravanan V. S.
Published: March 2024

Demand for lighter materials with the right qualities is unavoidable in the present era of engineering. Compacted graphite iron is a type of cast iron gaining momentum nowadays in foundries due to its distinct characteristics that fall between gray cast iron/flake graphite iron and spheroidal graphite iron. It becomes the right candidate to replace flake graphite iron in many applications. In this research, flake graphite iron (FC −30) and compacted graphite iron-300 grades were studied to enhance its properties through austempering heat treatment process. Initially, the as-cast (non-austempered) flake graphite iron and compacted graphite iron were subjected to microstructural study and mechanical testing. Subsequently, the flake graphite iron and compacted graphite iron were subjected to austempering heat treatment. The various austempering temperatures selected are 270, 320, and 370 °C for different soaking time periods of 30, 60, 90, and 120 min. As cast flake graphite iron specimen (FC-30) exhibited lesser tensile strength (293 N/mm2) than as cast compacted graphite iron (528 N/mm2) and austempered compacted graphite iron (652 N/mm2). With respect to hardness measurement, austempered compacted graphite iron specimens yielded higher hardness of up to 415 BHN. However, the compacted graphite iron specimen austempered at 370 °C for 90 min measured an optimum hardness value of 373 BHN and tensile strength of 630 N/mm2 with less retained austenite (0.3%). This hardness value is considered to be more suitable in machining operation for making hydraulic directional control valves exposed to constant abrasion.
Tuberculosis preventive treatment uptake among adults living with human immunodeficiency virus: Analysis of Zimbabwe population-based human immunodeficiency virus impact assessment 2020
Authors: Maphosa Talent , Mirkovic Kelsey , Weber Rachel A. , Musuka Godfrey , Mapingure Munyaradzi P. , Ershova Julia , Laws Rebecca , Dobbs Trudy , Coggin William , Sandy Charles , Apollo Tsitsi , Mugurungi Owen , Melchior Michael , Farahani Mansoor S.
Published: March 2024

Background

Tuberculosis remains the leading cause of death by an infectious disease among people living with HIV (PLHIV). TB Preventive Treatment (TPT) is a cost-effective intervention known to reduce morbidity and mortality. We used data from ZIMPHIA 2020 to assess TPT uptake and factors associated with its use.

Methodology

ZIMPHIA a cross-sectional household survey, estimated HIV treatment outcomes among PLHIV aged ≥15 years. Randomly selected participants provided demographic and clinical information. We applied multivariable logistic regression models using survey weights. Variances were estimated via the Jackknife series to determine factors associated with TPT uptake.

Results

The sample of 2419 PLHIV ≥15 years had 65% females, 44% had no primary education, and 29% lived in urban centers. Overall, 38% had ever taken TPT, including 15% currently taking TPT. Controlling for other variables, those screened for TB at last HIV-related visit, those who visited a TB clinic in the previous 12 months, and those who had HIV viral load suppression were more likely to take TPT.

Conclusion

The findings show suboptimal TPT coverage among PLHIV. There is a need for targeted interventions and policies to address the barriers to TPT uptake, to reduce TB morbidity and mortality among PLHIV.
Bronchopulmonary Dysplasia in a Tertiary Level Neonatal Unit of North India: Risk Factors and Outcome: A Case-control Study
Authors: Mishra Pragya , Tripathi Shalini , Sharma Akhil , Sonkar Gyanendra Kumar , Kumar Mala , Singh SN
Published: March 2024

Background

Bronchopulmonary dysplasia (BPD) in preterm neonates is a dreadful complication that increases the length of neonatal intensive care unit (NICU) stay, increases the cost of treatment, and poses long-term respiratory morbidity.

Methods

This was a case-control study to determine risk factors for BPD among preterm neonates (gestational age <32 weeks). Also, the proportion of BPD neonates developing secondary pulmonary arterial hypertension (PAH), vitamin D levels, and their outcomes were studied.

Results

Of 70 neonates with a mean birth weight of 1392 ± 544.28 grams and a mean gestational age of 30.14 ± 1.12 weeks, 35 cases of BPD (mild 42%, moderate 27%, severe 31%) and 35 controls were enrolled. After multivariate analysis, SGA (adjusted odds ratio [AOR] 12.6 with 95% CI 1.5-109.3; 0.022), lack of antenatal steroids (AOR 9.4 with 95% CI 1.8-50.7; 0.009), mechanical ventilation [MV] within the first 48 hours of life (AOR 8.7 with 95% CI 1.4-54.1; 0.021), and lack of surfactant administration (AOR 16.5% CI 3-89.1; 0.005) were independent risk factors. No significant difference was reported in vitamin D levels between BPD and non-BPD neonates (33.89 ± 22.50 ng/mL vs. 27.00 ± 8.17 ng/mL; 0.356). 14.3 % of BPD neonates expired, and 23% developed PAH. Neonates had a longer NICU stay than controls (46.66 ± 7.96 vs. 21 ± 8.82 days; <0.001)

Conclusion

We found SGA, lack of antenatal steroids, MV, and lack of surfactant administration to be independent risk factors for BPD. BPD neonates had dismal outcomes (one-fourth expired and left against medical advice), and one-fifth had PAH among survivors, increasing the length of their NICU stay.
Early Recognition and Institution of Treatment is Associated with a Good Prognosis in Peripheral Ischemic Lesions in Rheumatic Diseases
Authors: Dhakad Urmila , Mehta Pankti , Kishor Kriti
Published: March 2024

Introduction:

Peripheral ischemic lesions in rheumatic diseases have variable presentations, prognoses and outcomes that have not been well studied in published literature. The present study aimed to investigate the clinical presentation, aetiology, prognosis and outcomes of peripheral ischemic lesions in rheumatic diseases.

Material and methods:

A medical records review of all patients who presented with peripheral ischemic lesions was conducted in the Department of Clinical Immunology and Rheumatology of a tertiary care institution in Northern India. Data from March 2013 to December 2017 was collected in the form of demographic and clinical details, investigations, treatment and outcomes.

Results:

Of 103 patients that presented with peripheral ischemic lesions, 80 (77.6%) had an underlying rheumatic disease. In the group with rheumatic causes, the mean age was 29.31 years, and the majority (87%) presented in the winter season. The most common rheumatic cause was vasculitis (55%) followed by systemic sclerosis (17.5%), systemic lupus erythematosus (15%) and primary antiphospholipid antibody syndrome (6, 7.5%). Amputation (either surgical or auto-amputation) was observed in 55% of the cases, while the remaining recovered completely or near completely with medical treatment.

Conclusions:

Peripheral ischemic lesions may present as the initial or predominant manifestation of rheumatic disease with vasculitis being the most common cause. Late referral or presentation to the hospital, delayed specific management and presentation as gangrene resulted in poorer outcomes in these patients.
A recessive CLN3 variant is responsible for delayed-onset retinal degeneration in Hereford cattle
Authors: Reith Rachel R. , Batt Mackenzie C. , Fuller Anna M. , Meekins Jessica M. , Diehl Kathryn A. , Zhou You , Bedwell Patrick S. , Ward Jack A. , Sanders Stacy K. , Petersen Jessica L. , Steffen David J.
Published: March 2024

Thirteen American Hereford cattle were reported blind with presumed onset when ~12-mo-old. All blind cattle shared a common ancestor through both the maternal and paternal pedigrees, suggesting a recessive genetic origin. Given the pedigree relationships and novel phenotype, we characterized the ophthalmo-pathologic changes associated with blindness and identified the responsible gene variant. Ophthalmologic examinations of 5 blind cattle revealed retinal degeneration. Histologically, 2 blind cattle had loss of the retinal photoreceptor layer. Whole-genome sequencing (WGS) of 7 blind cattle and 9 unaffected relatives revealed a 1-bp frameshift deletion in ceroid lipofuscinosis neuronal 3 ( CLN3; chr25 g.26043843del) for which the blind cattle were homozygous and their parents heterozygous. The identified variant in exon 16 of 17 is predicted to truncate the encoded protein (p. Pro369Argfs*8) battenin, which is involved in lysosomal function necessary for photoreceptor layer maintenance. Of 462 cattle genotyped, only blind cattle were homozygous for the deletion. A query of WGS data of > 5,800 animals further revealed that the variant was only observed in related Hereford cattle. Mutations in CLN3 are associated with human juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease, which results in early-onset retinal degeneration and lesions similar to those observed in our cases. Our data support the frameshift variant of CLN3 as causative of blindness in these Hereford cattle, and provide additional evidence of the role of this gene in retinal lesions, possibly as a model for human non-syndromic JNCL.
The Gut Feeling of Rational Acting: Differentiation in Cognitive Strategies Within Commercial and Recreational Sellers in Hybrid Digital Social Media Markets
Authors: Demant Jakob , Nexø Louise Anker
Published: March 2024

In the realm of cybercrime, technologies that facilitate illicit activities also produce uncertainties based on the hybridity between digital communication and offline presence. Social media platforms have blurred the lines between types of drug sellers, bringing the recreational and the commercial into the same marketplace. In the Nordic data used in this paper, 52 text-based qualitative interviews with recreational and commercial sellers are analyzed via process and variance analysis to identify the relationship between cognitive strategies and seller positions. We ask how sellers’ decision-making processes differ and intersect. Theoretically, we use cognitive sociology to enrich understanding of culture, trust, and rational decision-making in this context. Our findings reveal that recreational sellers often adopt a low-risk, low-gain strategy rooted in cognitive biases, reflecting the recreational nature of their engagement. In contrast, commercially competent sellers employ more complex cognitive strategies, including gut feelings, thus adjusting their decisions with less reliance on initial assessments, leading to a more calculated approach with higher risk tolerance. We conclude with a discussion of intervention strategies; here, we argue for the need for a dual strategy that targets and capitalizes on the differences in cognitive biases in an effective way that poses less harm to recreational sellers.
Wife-Beating Endorsements Among African Youths: Current Prevalence and Predictors in 14 Sub-Saharan African Countries From 2015 to 2021
Authors: Ola Bamidele Emmanuel
Published: March 2024

This study investigates the prevalence and predictors of wife-beating endorsements among never-in-union male and female African youths, aged 15–24 years. Demographic and Health Survey data from 14 Sub-Saharan African countries (female = 55,387; male = 29,128) were analyzed using multiple logistic regression analyses. Approximately 37% of male and 42% of female African youths justified wife-beating, ranging from Mali (female = 71.1%, male = 58.7%) to Malawi (female = 21.4%, male = 22.3%). Young age, low education, limited Internet access, poverty, and rural residence were commonly associated with acceptance. Eliminating violence against women in Africa requires timely and adequate interventions.
Novel pathogenic variants of SLC38A8 gene and literature review
Authors: Ren Xiaofang , Huang Lijuan , Cheng Shan , Wang Jing , Li Ningdong
Published: March 2024

Purpose

This study aimed to analyze the clinical and genetic characteristics of 6 Chinese patients with foveal hypoplasia (FH) caused by the variants of solute carrier family 38 member 8 ( SLC38A8), and to describe the genotype and phenotype of SLC38A8 variants from previous literature.

Methods

All subjects underwent comprehensive ophthalmic examinations. Optical coherence tomography (OCT) was performed to evaluate the structural grade of FH. Pathogenic variants of SLC38A8 gene were identified using panel-based next-generation sequencing and direct Sanger sequencing techniques. Further, all previously reported cases of SLC38A8 variants were re-analyzed together with the novel ones identified in this study.

Results

Nystagmus and FH were present in 6 patients with variants of SLC38A8 gene, accompanied by a normal anterior segment. Grade 4 FH was identified in 4 patients. A total of 12 variants of SLC38A8 gene were identified, including 9 novel variants. Systematical analysis revealed that half of the variants (30/60) were missense, the majority of which (23/30) were distributed in the transmembrane (TM) domains. Grade 4 FH was detected in the majority of patients (66%, 23/35). There was no statistical difference in the clinical features between the subgroups of patients with 0, 1 and 2 missense variants.

Conclusion

Severe arrest of foveal development was identified in patients with variants of SLC38A8. This study provides a brief summary of the clinical and genetic characteristics of the pathogenic SLC38A8 variants, which is helpful in the differentiation diagnosis of FH.
Measuring depression and anxiety in autistic college students: A psychometric evaluation of the PHQ-9 and GAD-7
Authors: Robeson Mackenzie , Brasil Kyle M , Adams Haley C , Zlomke Kimberly R
Published: March 2024

Anxiety, depression, and suicidality are major concerns among college students, though less is known about these constructs in autistic college students. Given the rising number of autistic individuals entering post-secondary education, adequate measurement and diagnosis of anxiety, depression, and suicidality is necessary to provide clinical care to this population. While the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) are commonly used in university settings, these instruments have not been psychometrically evaluated in autistic college students. The current study examines the differential psychometric properties of the GAD-7 and PHQ-9 utilizing invariance testing via structural equation modeling in a sample of self-identified autistic ( n = 477) and non-autistic ( n = 429) university students. Results showed that although the GAD-7 is invariant, the PHQ-9 was mostly invariant, with one item displaying non-invariance. Specifically, the PHQ-9 item assessing suicidality was found to be non-invariant at the metric level, indicating that autistic and non-autistic college students interpret this question differently. Future investigators should continue to assess the appropriateness of using common screening measures, originally created for non-autistic people, in autistic populations.

Lay abstract

Anxiety, depression, and suicidality are major concerns among college students, though less is known about these constructs in autistic college students. Given the rising number of autistic individuals entering college, adequate screening and diagnosis of mental health difficulties is necessary to provide care to this population. For example, despite widespread usage of the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), it is unknown if the two instruments accurately measure depression and anxiety the same way between non-autistic and autistic individuals. Thus, the current study was the first to examine how these instruments measure depression and anxiety symptoms in autistic versus non-autistic college students. Utilizing tests of construct measurement in a sample of autistic ( n = 477) and non-autistic ( n = 429) university students aged 18–29, results showed that while the GAD-7 and PHQ-9 appear to be accurately capturing anxiety and depression in autistic college students, the PHQ-9 item assessing suicidality was found to be measuring different things. This indicates that autistic college students are not interpreting this question the way non-autistic students are, and thus, the measure is failing to capture suicidality in autistic people. Future investigators should continue to assess the appropriateness of using common screening measures, originally created by non-autistic people, in autistic populations.
Determination of In Vitro and In Vivo Effects of Taxifolin and Epirubicin on Epithelial–Mesenchymal Transition in Mouse Breast Cancer Cells
Authors: Ocak Muhammet , Usta Duygu Deniz , Arik Erol Gokce Nur , Kaplanoglu Gulnur Take , Konac Ece , Yar Saglam Atiye Seda
Published: March 2024

Background: One of the most significant characteristics of cancer is epithelial–mesenchymal transition and research on the relationship between phenolic compounds and anticancer medications and epithelial–mesenchymal transition is widespread. Methods: In order to investigate the potential effects of Taxifolin on enhancing the effectiveness of Epirubicin in treating breast cancer, specifically in 4T1 cells and an allograft BALB/c model, the effects of Taxifolin and Epirubicin, both individually and in combination, were examined. Cell viability assays and cytotoxicity assays in 4T1 cells were performed. In addition, 4T1 cells were implanted into female BALB/c mice to conduct in vivo studies and evaluate the therapeutic efficacy of Taxifolin and Epirubicin alone or in combination. Tumor volumes and histological analysis were also assessed in mice. To further understand the mechanisms involved, we examined the messenger RNA and protein levels of epithelial–mesenchymal transition-related genes, as well as active Caspase-3/7 levels, using quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assays, respectively. Results: In vitro results demonstrated that the coadministration of Taxifolin and Epirubicin reduced cell viability and cytotoxicity in 4T1 cell lines. In vivo, coadministration of Taxifolin and Epirubicin suppressed tumor growth in BALB/c mice with 4T1 breast cancer cells. Additionally, this combination treatment significantly increased the levels of active caspase-3/7 and downregulated the messenger RNA and protein levels of N-cadherin, β-catenin, vimentin, snail, and slug, but upregulated the E-cadherin gene. It significantly decreased the messenger RNA levels of the Zeb1 and Zeb2 genes. Conclusion: The in vitro and in vivo results of our study indicate that the concurrent use of Epirubicin with Taxifolin has supportive effects on breast cancer treatment.
Hydrodynamic performance of windsurfing boards with bottom modifications at high speed in calm water
Authors: Matveev Konstantin I
Published: March 2024

Hydrodynamic performance of windsurfing boards is greatly affected by geometrical details of their bottom surfaces. In this study, computational fluid dynamics is applied to simulate flow around boards with several bottom modifications, including deadrise, rocker, step, wedge, and wing-tail profile. These simulations are conducted in steady-state, calm-water regimes at high planing speeds. It is found that at similar board trim angles and vertical positions, the largest lift is produced by setups with the bottom wedge and the wing-tail profile that enhance the downward deflection of the incident water flow. The highest lift-drag ratio is achieved by the variants with the bottom step and wedge that enable partial air ventilation of the bottom surface, which leads to reduced wetted surface and lower frictional resistance. The center of lift is located more forward on the rocker and stepped configurations, while it is positioned more rearward for the wedge and wing-tail setups. The obtained results can be used for guiding board designs aimed at maximizing the board hydrodynamic performance in calm water.
Clinical characteristics and surgical outcomes of low-grade epilepsy-associated brain tumors
Authors: Kuang Suhui , Zhang Shaohui , Cui Zhiqiang , Ge Ming , Yuan Liu , Wang Jiaqi , Wei Zhirong , Xu Jinshan , Zhai Feng , Liang Shuli
Published: March 2024

Background:

Low-grade epilepsy-associated brain tumors (LEATs) are found to be the second most common lesion-related epilepsy. Malignant potential of LEATs is very low and the overall survival is good, so the focus of treatment is focused more on seizure outcome rather than oncological prognosis.

Objectives:

This study was conducted to evaluate the risk factors of seizure outcomes after resection in patients with LEATs.

Design:

A retrospective study.

Methods:

A retrospective analysis of patients with LEATs who underwent resective surgery in our three epilepsy centers between October 2010 and April 2023 with a minimum follow-up of 1 year. Demography, clinical characters, neurophysiology, and molecular neuropathology were assessed for association with postoperative seizure outcomes at 1-, 2-, and 5-year follow-up. Synthetic minority oversampling technique (SMOTE) algorithm model was performed to handle the imbalance of data distribution. Gaussian Naïve Bayes (GNB) algorithms were created as a basis for classifying outcomes according to observation indicators.

Results:

A total of 111 patients were enrolled in the cohort. The most common pathology was ganglioglioma ( n = 37, 33.3%). The percentage of patients with seizure freedom was 91.0% (101/111) at 1-year follow-up, 87.5% (77/88) at 2-year follow-up, and 79.1% (53/67) at 5-year follow-up. Partial resection had a significantly poor seizure outcome compared to total resection and supratotal resection ( p < 0.05). The epileptiform discharge on post-resective intraoperative electrocorticography (ECoG) or postoperative scalp electroencephalography (EEG) were negative factors on postoperative seizure freedom at 1-, 2-, or 5-year follow-ups ( p < 0.05). The area under the receiver-operating characteristic curve value of the GNB-SMOTE model was 0.95 (95% CI, 0.876–1.000), 0.892 (95% CI, 0.656–0.934), and 0.786 (95% CI, 0.491–0.937) at 1-, 2-, and 5-year follow-up, respectively.

Conclusion:

The partial resection, post-resective intraoperative ECoG, and postoperative scalp EEG were valuable indicators of poor seizure outcomes. The utilization of post-resective intraoperative ECoG is beneficial to improve seizure outcomes. Based on the data diversity and completeness of three medical centers, a multivariate correlation analysis model was established based on GNB algorithm.
Network Pharmacology Approach and Partial Experimental Validation of Aidi Injection Solution for the Treatment of Colorectal Cancer
Authors: Yu Wentao , Weng Yinhua , Wang Jiawei , Gao Yifei , Li Yaqi , Xie Chichu , Jian Zhiyuan
Published: March 2024

Purpose

The objective of this research was to employ network pharmacology to analyze and identify the key active components and target points of action of Aidi injection in relation to colorectal cancer. Additionally, this study aimed to experimentally validate the mechanism of action of hinokinin in treating colorectal cancer.

Methods

This study employed a network pharmacology methodology to identify the primary components and action targets of Aidi injection in public databases; a similar approach was used to identify effective targets for colorectal cancer treatment. The protein‒protein interaction network, along with gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, facilitated the prediction of central targets and pathways by which Aidi injection combats colorectal cancer. Molecular docking techniques were harnessed to sift through drugs and their targets for high binding affinity. Experimental validation was carried out to corroborate the findings derived from network pharmacology.

Results

We identified 37 active constituents of Aidi injection (ADI), 701 potential targets, 768 colorectal cancer (CRC) targets, and 111 overlapping targets. The anti-CRC efficacy of ADI seems to be associated with several pathways: cancer pathways, EGFR tyrosine kinase inhibitor resistance, proteoglycans in cancer, endocrine resistance, central carbon metabolism in cancer, chemo-oncogenic receptor initiation, cancer-specific microRNAs, and signaling pathways such as PI3K-Akt, mitogen-activated protein kinase, prolactin, FoxO, and Ras. Predominantly, ADI exhibited activity against key markers such as EGFR, ERBB2, HSP90AA1, mTOR, HIF1A, CCND1, JUN, AKT1, SRC, and STAT3 to mitigate CRC. Furthermore, Hinokinin has been shown to curtail the proliferation of colorectal cancer cells, amplify apoptosis, and modulate the expression of the mTOR protein.

Conclusion

Through network pharmacology, we identified 13 shared targets associated with colorectal cancer. Subsequent experimental validation revealed that hinokinin can curtail the proliferation of colorectal cancer cells and enhance their apoptosis, primarily by modulating mTOR expression.
Predicting early gastric cancer risk using machine learning: A population-based retrospective study
Authors: Ke Xing , Cai Xinyu , Bian Bingxian , Shen Yuanheng , Zhou Yunlan , Liu Wei , Wang Xu , Shen Lisong , Yang Junyao
Published: March 2024

Background

Early detection and treatment are crucial for reducing gastrointestinal tumour-related mortality. The diagnostic efficiency of the most commonly used diagnostic markers for gastric cancer (GC) is not very high. A single laboratory test cannot meet the requirements of early screening, and machine learning methods are needed to aid the early diagnosis of GC by combining multiple indicators.

Methods

Based on the XGBoost algorithm, a new model was developed to distinguish between GC and precancerous lesions in newly admitted patients between 2018 and 2023 using multiple laboratory tests. We evaluated the ability of the prediction score derived from this model to predict early GC. In addition, we investigated the efficacy of the model in correctly screening for GC given negative protein tumour marker results.

Results

The XHGC20 model constructed using the XGBoost algorithm could distinguish GC from precancerous disease well (area under the receiver operating characteristic curve [AUC] = 0.901), with a sensitivity, specificity and cut-off value of 0.830, 0.806 and 0.265, respectively. The prediction score was very effective in the diagnosis of early GC. When the cut-off value was 0.27, and the AUC was 0.888, the sensitivity and specificity were 0.797 and 0.807, respectively. The model was also effective at evaluating GC given negative conventional markers (AUC = 0.970), with the sensitivity and specificity of 0.941 and 0.906, respectively, which helped to reduce the rate of missed diagnoses.

Conclusions

The XHGC20 model established by the XGBoost algorithm integrates information from 20 clinical laboratory tests and can aid in the early screening of GC, providing a useful new method for auxiliary laboratory diagnosis.