bluuebunny/crossref_metadata_2025 huggingface dataset:
Response rates and associated factors after a multicomponent intervention in frail older adults with diabetes
Authors: Álvarez-Bustos Alejandro , Laosa Olga , Marzetti Emanuele , Carnicero Jose Antonio , Castro-Rodriguez Marta , Landi Francesco , Sinclair Alan J , Rodriguez-Mañas Leocadio
Published: January 2024

Background

Type 2 diabetes mellitus (T2DM) and frailty are associated with functional decline in older population.

Objective

To explore the individual response to a multimodal intervention on functional performance.

Design

A cluster-randomised multicentre clinical trial.

Setting

Outpatients in hospital or primary care.

Subjects

843 (77.83 years, 50.65% men) prefrail and frail individuals ≥70 years with T2DM.

Methods

Participants were allocated to usual care group (UCG) or a multicomponent intervention group (IG): 16-week progressive resistance training, seven nutritional and diabetological educational sessions and achievement of glycated haemoglobin (7–8%) and blood pressure (<150 mmHg) targets. Functional performance was assessed with the Short Physical Performance Battery (SPPB) at 1 year. We used multivariate binomial and multinomial logistic regression models to explore the effect of the IG, and adherence on the outcomes studied, in several adjusted models.

Results

53.7% in the IG versus 38.0% in the UCG improved by at least 1 point in their SPPB score [OR (95% CI): 2.07 (1.43, 2.98), P value <0.001]. Age, SPPB score and number of frailty criteria met decreased the probability of improving the SPPB score. Factors associated with worsening were pertaining to IG (decreased), age, SPPB score and the number of frailty criteria (increased). An adherence ≥84% was needed to achieve benefits, reaching the peak in the probability of improving SPPB when this was ≥85% [OR(95%CI): 2.38 (1.29, 4.79), P value 0.014].

Conclusions

Factors predicting the likelihood of improvement in a multimodal programme in pre-frail and frail older adults with diabetes are age, basal SPPB score, the number of frailty criteria and adherence.
A non-inferiority randomized controlled trial comparing nebulized ketamine to intravenous morphine for older adults in the emergency department with acute musculoskeletal pain
Authors: Kampan Sirasa , Thong-on Kwannapa , Sri-on Jiraporn
Published: January 2024

Objective

Our study aimed to investigate the analgesic efficacy of nebulized ketamine in managing acute moderate-to-severe musculoskeletal pain in older emergency department (ED) patients compared with intravenous (IV) morphine.

Methods

This was a non-inferiority, double-blind, randomized controlled trial conducted at a single medical centre. The patients aged 65 and older, who presented at the ED musculoskeletal pain within 7 days and had a pain score of 5 or more on an 11-point numeric rating scale (NRS), were included in the study. The outcomes were a comparison of the NRS reduction between nebulized ketamine and IV morphine 30 minutes after treatment, incidence of adverse events and rate of rescue therapy.

Results

The final study included 92 individuals, divided equally into two groups. At 30 minutes, the difference in mean NRS between the nebulized ketamine and IV morphine groups was insignificant (5.2 versus 5.7). The comparative mean difference in the NRS change from baseline between nebulized ketamine and IV morphine [−1.96 (95% confidence interval—CI: −2.45 to −1.46) and −2.15 (95% CI: −2.64 to −1.66) = 0.2 (95% CI: −0.49 to 0.89)] did not exceed the non-inferiority margin of 1.3. The rate of rescue therapy did not differ between the groups. The morphine group had considerably higher incidence of nausea than the control group (zero patients in the ketamine group versus eight patients (17.4%) in the morphine group; P = 0.006).

Conclusions

Nebulized ketamine has non-inferior analgesic efficacy compared with IV morphine for acute musculoskeletal pain in older persons, with fewer adverse effects.
Association of chronic conditions and physical multimorbidity with new-onset incontinence in a nationwide prospective cohort study of older adults ≥ 50 years in China
Authors: Li Haibin , Zou Xinye , Zhang Ruolin , Zou Siyu , Qian Frank , Zheng Jin , Xiao Angela Y , Guo Xiuhua
Published: January 2024

Background

The relationship between multimorbidity (i.e. ≥ 2 chronic conditions) and incontinence (i.e. urinary and/or faecal incontinence) is underexplored. This study investigated the association between multimorbidity and incident incontinence in Chinese adults aged ≥50 years.

Methods

Data from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study were used. The association between 12 chronic conditions, multimorbidity and new-onset incontinence was analysed using weighted logistic regression models. Mediation analysis was conducted to explore the potential mediators (self-reported health, subjective memory, depressive symptoms, disability, cognitive function, handgrip strength, mobility limitations, medications and frailty status) between multimorbidity and incontinence.

Findings

Among 9,986 individuals aged ≥50 years who were continent at baseline, 5.3% (n = 521) were newly incontinent 4 years later (incident cases). The risk of incident incontinence increased with physical multimorbidity (OR 2.04, 95% CI 1.62–2.57). Compared to no chronic condition, having 1, 2, 3 and ≥ 4 chronic conditions were associated with incident incontinence with OR (95% CI): 1.41 (1.01–1.97), 1.74 (1.24–2.44), 2.82 (1.93–4.12) and 3.99 (2.29–6.95), respectively. The association between multimorbidity and incontinence was mediated by self-reported health (41.2%), medications (26.6%), mobility limitations (20.9%), depressive symptoms (12.8%), disability (11.6%), subjective memory (8.7%) and frailty status (8.3%).

Conclusion

This longitudinal study found that physical multimorbidity and specific chronic conditions may increase the risk of new-onset incontinence among Chinese adults aged ≥50 years. Self-reported health, medications and mobility limitations seemed to be important intermediate conditions between multimorbidity and incident incontinence.
Interventions aimed to increase average 24-h systolic blood pressure reduce blood pressure drops in patients with reflex syncope and orthostatic intolerance
Authors: Groppelli Antonella , Rivasi Giulia , Fedorowski Artur , de Lange Frederik J , Russo Vincenzo , Maggi Roberto , Capacci Marco , Nawaz Sara , Comune Angelo , Bianchi Lorenzo , Zambon Antonella , Soranna Davide , Ungar Andrea , Parati Gianfranco , Brignole Michele
Published: January 2024

Aims

Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops.

Methods and results

This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5 mmHg (P < 0.0001). The number of SBP drops <90 and <100 mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose–response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around ∼15 mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67).

Conclusion

In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13 mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions.

ClincalTrials.gov identifier: NCT05729724
Extended cost-effectiveness analysis of interventions to improve uptake of diabetes services in South Africa
Authors: Fraser Heather L , Feldhaus Isabelle , Edoka Ijeoma P , Wade Alisha N , Kohli-Lynch Ciaran N , Hofman Karen , Verguet Stéphane
Published: January 2024

The rising prevalence of diabetes in South Africa (SA), coupled with significant levels of unmet need for diagnosis and treatment, results in high rates of diabetes-associated complications. Income status is a determinant of utilization of diagnosis and treatment services, with transport costs and loss of wages being key barriers to care. A conditional cash transfer (CCT) programme, targeted to compensate for such costs, may improve service utilization. We applied extended cost-effectiveness analysis (ECEA) methods and used a Markov model to compare the costs, health benefits and financial risk protection (FRP) attributes of a CCT programme. A population was simulated, drawing from SA-specific data, which transitioned yearly through various health states, based on specific probabilities obtained from local data, over a 45-year time horizon. Costs and disability-adjusted life years (DALYs) were applied to each health state. Three CCT programme strategies were simulated and compared to a ‘no programme’ scenario: (1) covering diagnosis services only; (2) covering treatment services only; (3) covering both diagnosis and treatment services. Cost-effectiveness was reported as incremental net monetary benefit (INMB) using a cost-effectiveness threshold of USD3015 per DALY for SA, while FRP outcomes were reported as catastrophic health expenditure (CHE) cases averted. Distributions of the outcomes were reported by income quintile and sex. Covering both diagnosis and treatment services for the bottom two quintiles resulted in the greatest INMB (USD22 per person) and the greatest CHE cases averted. There were greater FRP benefits for women compared to men. A CCT programme covering diabetes diagnosis and treatment services was found to be cost-effective, when provided to the poorest 40% of the SA population. ECEA provides a useful platform for including equity considerations to inform priority setting and implementation policies in SA.
Prediction Models for Adverse Drug Reactions During Tuberculosis Treatment in Brazil
Authors: Ridolfi Felipe , Amorim Gustavo , Peetluk Lauren S , Haas David W , Staats Cody , Araújo-Pereira Mariana , Cordeiro-Santos Marcelo , Kritski Afrânio L , Figueiredo Marina C , Andrade Bruno B , Rolla Valeria C , Sterling Timothy R ,   for the Regional Prospective Observational Research in Tuberculosis (RePORT)–Brazil Consortium, Benjamin Aline , Sant’Anna Flavia M , de Oliveira Jamile Garcia , Marin João , Rezende Adriana , Carvalho Anna Cristina , Rocha Michael , Nogueira Betânia , Brito Alexandra , Spener Renata , Turner Megan
Published: January 2024

Background

Tuberculosis (TB) treatment–related adverse drug reactions (TB-ADRs) can negatively affect adherence and treatment success rates.

Methods

We developed prediction models for TB-ADRs, considering participants with drug-susceptible pulmonary TB who initiated standard TB therapy. TB-ADRs were determined by the physician attending the participant, assessing causality to TB drugs, the affected organ system, and grade. Potential baseline predictors of TB-ADR included concomitant medication (CM) use, human immunodeficiency virus (HIV) status, glycated hemoglobin (HbA1c), age, body mass index (BMI), sex, substance use, and TB drug metabolism variables (NAT2 acetylator profiles). The models were developed through bootstrapped backward selection. Cox regression was used to evaluate TB-ADR risk.

Results

There were 156 TB-ADRs among 102 of the 945 (11%) participants included. Most TB-ADRs were hepatic (n = 82 [53%]), of moderate severity (grade 2; n = 121 [78%]), and occurred in NAT2 slow acetylators (n = 62 [61%]). The main prediction model included CM use, HbA1c, alcohol use, HIV seropositivity, BMI, and age, with robust performance (c-statistic = 0.79 [95% confidence interval {CI}, .74–.83) and fit (optimism-corrected slope and intercept of −0.09 and 0.94, respectively). An alternative model replacing BMI with NAT2 had similar performance. HIV seropositivity (hazard ratio [HR], 2.68 [95% CI, 1.75–4.09]) and CM use (HR, 5.26 [95% CI, 2.63–10.52]) increased TB-ADR risk.

Conclusions

The models, with clinical variables and with NAT2, were highly predictive of TB-ADRs.
On sheaves on semicartesian quantales and their truth values
Authors: Luiza Tenorio Ana , de Andrade Mendes Caio , Luiz Mariano Hugo
Published: January 2024

In this paper, we introduce a new definition of sheaves on semicartesian quantales, providing first examples and categorical properties. We note that our sheaves are similar to the standard definition of a sheaf on a locale; however, we prove that in general it is not an elementary topos—since the lattice of external truth values of $Sh(Q)$, $Sub(1)$, is canonically isomorphic to the quantale $Q$—placing this paper as part of a greater project towards a monoidal (not necessarily cartesian) closed version of elementary topos. To start the study the logical aspects of the category of sheaves we are introducing, we explore the nature of the ‘internal truth value objects’ in such sheaves categories. More precisely, we analyse two candidates for subobject classifier for different subclasses of commutative and semicartesian quantales.
The extremely young planetary nebula M 3-27: an analysis of its evolution, physical conditions, and abundances
Authors: Ruiz-Escobedo Francisco , Peña Miriam , Beltrán-Sánchez Ana Valeria
Published: January 2024

Spectrophotometric data of the young planetary nebula M 3-27, from 2004 to 2021, are presented and discussed. We corroborate that the H i Balmer lines present features indicating they are emitted by the central star, therefore He i lines were used to correct line fluxes by effects of reddening. Important variability on the nebular emission lines between 1964 and 2021, probably related to density changes in the nebula, is reported. Diagnostic diagrams to derive electron temperatures and densities have been constructed. The nebula shows a very large density contrast with an inner density of the order of 107 cm−3 and an outer density of about 103–104 cm−3. With these values of density, electron temperatures of 16 000–18 000 K have been found from collisionally excited lines. Because the central star emits in the H+ lines, ionic abundances relative to He+ were calculated from collisionally excited and recombination lines, and scaled to H+ by considering that He+/H+ = He/H = 0.11. Abundance discrepancy factor (O+2) values were also determined. Total abundance values obtained indicate sub-solar abundances, similar to what is found in other comparable objects like IC 4997.
Genetic regulation of self-organizing azimuthal canopy orientations and their impacts on light interception in maize
Authors: Zhou Yan , Kusmec Aaron , Schnable Patrick S
Published: January 2024

The efficiency of solar radiation interception contributes to the photosynthetic efficiency of crop plants. Light interception is a function of canopy architecture, including plant density; leaf number, length, width, and angle; and azimuthal canopy orientation. We report on the ability of some maize (Zea mays) genotypes to alter the orientations of their leaves during development in coordination with adjacent plants. Although the upper canopies of these genotypes retain the typical alternate-distichous phyllotaxy of maize, their leaves grow parallel to those of adjacent plants. A genome-wide association study (GWAS) on this parallel canopy trait identified candidate genes, many of which are associated with shade avoidance syndrome, including phytochromeC2. GWAS conducted on the fraction of photosynthetically active radiation (PAR) intercepted by canopies also identified multiple candidate genes, including liguleless1 (lg1), previously defined by its role in ligule development. Under high plant densities, mutants of shade avoidance syndrome and liguleless genes (lg1, lg2, and Lg3) exhibit altered canopy patterns, viz, the numbers of interrow leaves are greatly reduced as compared to those of nonmutant controls, resulting in dramatically decreased PAR interception. In at least the case of lg2, this phenotype is not a consequence of abnormal ligule development. Instead, liguleless gene functions are required for normal light responses, including azimuth canopy re-orientation.
Positive affect disrupts neurodegeneration effects on cognitive training plasticity in older adults
Authors: Anthony Mia , Turnbull Adam , Tadin Duje , Lin F Vankee
Published: January 2024

Cognitive training for older adults varies in efficacy, but it is unclear why some older adults benefit more than others. Positive affective experience (PAE), referring to high positive valence and/or stable arousal states across everyday scenarios, and associated functional networks can protect plasticity mechanisms against Alzheimer’s disease neurodegeneration, which may contribute to training outcome variability. The objective of this study is to investigate whether PAE explains variability in cognitive training outcomes by disrupting the adverse effect of neurodegeneration on plasticity. The study’s design is a secondary analysis of a randomized control trial of cognitive training with concurrent real or sham brain stimulation (39 older adults with mild cognitive impairment; mean age, 71). Moderation analyses, with change in episodic memory or executive function as the outcome, PAE or baseline resting-state connectivity as the moderator and baseline neurodegeneration as the predictor are the methods used in the study. The result of the study is that PAE stability and baseline default mode network (DMN) connectivity disrupted the effect of neurodegeneration on plasticity in executive function but not episodic memory. The study concludes that PAE stability and degree of DMN integrity both explained cognitive training outcome variability, by reducing the adverse effect of neurodegeneration on cognitive plasticity. We highlight the need to account for PAE, brain aging factors and their interactions with plasticity in cognitive training.
Direct Reprogramming of Hepatocytes Into JAK/Stat-Dependent LGR5+ Liver Cells Able to Initiate Intrahepatic Cholangiocarcinoma
Authors: Chaker Diana , Desterke Christophe , Moniaux Nicolas , Bani Mohamed-Amine , Oudrhiri Noufissa , Faivre Jamila , Turhan Ali G , Bennaceur-Griscelli Annelise , Griscelli Frank
Published: January 2024

Somatic cells that have been partially reprogrammed by the factors Oct4, Sox2, Klf4, and cMyc (OSKM) have been demonstrated to be potentially tumorigenic in vitro and in vivo due to the acquisition of cancer-associated genomic alterations and the absence of OSKM clearance over time. In the present study, we obtained partially reprogrammed, SSEA1-negative cells by transducing murine hepatocytes with Δ1Δ3-deleted adenoviruses that expressed the 4 OSKM factors. We observed that, under long-term 2D and 3D culture conditions, hepatocytes could be converted into LGR5-positive cells with self-renewal capacity that was dependent on 3 cross-signaling pathways: IL6/Jak/Stat3, LGR5/R-spondin, and Wnt/β-catenin. Following engraftment in syngeneic mice, LGR5-positive cells that expressed the cancer markers CD51, CD166, and CD73 were capable of forming invasive and metastatic tumors reminiscent of intrahepatic cholangiocarcinoma (ICC): they were positive for CK19 and CK7, featured associations of cord-like structures, and contained cuboidal and atypical cells with dissimilar degrees of pleomorphism and mitosis. The LGR5+-derived tumors exhibited a highly vascularized stroma with substantial fibrosis. In addition, we identified pro-angiogenic factors and signaling pathways involved in neo-angiogenesis and vascular development, which represent potential new targets for anti-angiogenic strategies to overcome tumor resistance to current ICC treatments.
Utilizing Telenursing to Supplement Acute Care Nursing in an Era of Workforce Shortages
Authors: Schwartz Roberta L. , Hamlin Shannan K. , Vozzella Gail M. , Randle Lindsay N. , Klahn Steven , Maris Gabbi J. , Waterman Amy D.
Published: January 2024

Hospitals are experiencing a nursing shortage crisis that is expected to worsen over the next decade. Acute care settings, which manage the care of very complex patients, need innovations that lessen nurses' workload burden while ensuring safe patient care and outcomes. Thus, a pilot study was conducted to evaluate the feasibility of implementing a large-scale acute care telenurse program, where a hospital-employed telenurse would complete admission and discharge processes for hospitalized patients virtually. In 3 months, almost 9000 (67%) of patient admissions and discharges were conducted by an acute care telenurse, saving the bedside nurse an average of 45 minutes for each admission and discharge. Preliminary benefits to the program included more uninterrupted time with patients, more complete hospital admission and discharge documentation, and positive patient and nurse feedback about the program.
Disparities in the Receipt of Systemic Treatment in Metastatic Melanoma
Authors: Kakish Hanna , Pawar Omkar , Bhatty Maira , Doh Susan , Mulligan Kathleen M. , Rothermel Luke D. , Bordeaux Jeremy S. , Mangla Ankit , Hoehn Richard S.
Published: January 2024

Introduction:

In 2011, immunotherapy and targeted therapy revolutionized melanoma treatment. However, inequities in their use may limit the benefits seen by certain patients.

Methods:

We performed a retrospective review of patients in the National Cancer Database for patients with stage IV melanoma from 2 time periods: 2004–2010 and 2016–2020, distinguishing between those who received systemic therapy and those who did not. We investigated the rates and factors associated with treatment omission. We employed Kaplan-Meier analysis to explore the impact of treatment on overall survival.

Results:

A total of 19,961 patients met the inclusion criteria: 7621 patients were diagnosed in 2004–2010 and 12,340 patients in 2016–2020, of whom 54.9% and 28.3% did not receive systemic treatment, respectively. The rate of “no treatment” has decreased to a plateau of ∼25% in 2020. Median overall survival was improved with treatment in both time periods (2004–2010: 8.8 vs. 5.6 mo [P<0.05]; and 2016–2020: 25.9 vs. 4.3 mo [P<0.05]). Nonmedical factors associated with the omission of treatment in both periods included low socioeconomic status, Medicaid or no health insurance, and treatment at low-volume centers. In the period from 2016 to 2020, patients treated at nonacademic programs were also less likely to receive treatment.

Conclusions:

Systemic therapies significantly improve survival for patients with metastatic melanoma, but significant disparities exist with their receipt. Local efforts are needed to ensure all patients benefit from these revolutionary treatments.
Chinese Population Reference Curves for Ultrasound-Measured Amniotic Fluid Deepest Vertical Pocket in Dichorionic Twin Pregnancies, and Their Associations With Pregnancy Outcomes
Authors: Lyu Zhengxin , Wu Tianchen , Lu Shan , Yuan Pengbo , Zhao Yangyu , Wei Yuan
Published: January 2024

Objective

To establish the Chinese population's amniotic fluid deepest vertical pocket (DVP) reference curves for dichorionic twin pregnancies and to investigate DVP links with adverse perinatal outcomes.

Methods

This retrospective cohort study, conducted at Peking University Third Hospital from August 2011 to December 2020, used data from 375 women aged 20 to 45 years who had dichorionic twin pregnancies that were confirmed through first-trimester ultrasound. After exclusions, reference curves were developed using 318 women with 3,299 DVP scans, and the data analyzed included maternal demographics, pregnancy outcomes, ultrasound measurements, and neonatal information. DVPs were assessed via ultrasound at regular intervals and grouped by gestational age (GA) for analyses. Linear mixed models were used to create amniotic fluid reference curves. Associations between abnormalities and adverse perinatal outcomes were examined using Chi-squared or Fisher's exact tests. Logistic regression provided both crude and adjusted odds ratios, adjusting for pre-pregnancy weight, age, ethnicity, parity, and conception mode. Significance was set at P < 0.05 with 95% confidence intervals (CI), and the analyses were conducted using SPSS ver. 26.0 (IBM Corp., Armonk, NY) and SAS ver. 9.4 (SAS Institute Inc., Cary, NC, USA) software.

Results

DVP increased from the first trimester to a maximum at 26 weeks (95% confidence interval (CI), 2.7–8.3 cm for twin 1 and 2.8–7.9 cm for twin 2) and then decreased gradually toward term. Differences between twins 1 and 2 were significant after 26 weeks (95% CI for twin 1: 5.3, 5.5; 95% CI for twin 2: 4.4, 4.5; P < 0.010). Polyhydramnios of twin 1 increased the risk of large for GA. Oligohydramnios of twin 1 increased the risk of small for GA. Polyhydramnios of twin 2 increased the risk of small for GA, premature birth, and neonatal complications. Oligohydramnios of twin 2 increased the risk of preeclampsia, hypertensive disorder complicating pregnancy, and premature rupture of membranes.

Conclusion

Reference curves for twin amniotic fluid volumes vary by GA and differ between twins, with potential implications for pregnancy outcomes.
Modulation of canonical Wnt signaling regulates peribiliary mesenchymal identity during homeostasis and injury
Authors: Singh Serrena , Budiman Tifanny , Redmond David , Gupta Vikas
Published: January 2024

Background:

The matrix and associated mesenchyme of the extrahepatic bile ducts are distinct, which could drive diseases with a predilection for these ducts, such as primary sclerosing cholangitis. We aimed to understand the molecular drivers of peribiliary mesenchymal cell (PMC) identity in the extrahepatic bile ducts and dissect how this changed in the context of injury using an entirely in vivo approach with transcriptomic analysis.

Methods and Results:

Single-cell sequencing with a receptor-ligand analysis showed that PMCs had the most interactions with surrounding cells. Wnt4, Wnt5a, and Wnt7b were identified as the major ligands secreted from PMCs and cholangiocytes that interacted in both paracrine and autocrine fashion. Bile duct ligation caused an increase in all 3 Wingless/Integrated ligands and Axin2 with an associated increase in the transcription factors T-box transcription factor (Tbx)2 and Tbx3. Conversely, Indian hedgehog secretion decreased without an associated decrease in hedgehog signaling effectors. Loss of smoothened within PMCs did not impact hedgehog signaling effectors or cellular identity, whereas smoothened gain of function led to myofibroblast transdifferentiation with upregulation of Tbx2 and Tbx3 without injury. Loss of β-catenin caused a decrease in expression of all 3 Gli transcription factors and associated mesenchymal gene expression, which was phenocopied with compound Gli2 and Gli3 loss in uninjured PMCs. With injury, loss of β-catenin resulted in decreased myofibroblast transdifferentiation with reduced Tbx2 and Tbx3 expression.

Conclusions:

Our results show how modulation of canonical Wingless/Integrated signaling in PMCs is important for regulating basal mesenchymal gene expression and initiating a myogenic gene transcriptional program during injury. They also highlight reciprocating interactions between the hedgehog and Wingless/Integrated signaling pathways within PMCs.
Changing Course: Understanding the Legal Landscape of Race-Conscious Admission Practices and Implications to Diversity-Promoting Strategies in Higher Education
Authors: Noller Diana T. , Bañuelas Angela , Diallo Shannon
Published: January 2024

The 2023 US Supreme Court holding in Students for Fair Admissions, Inc. v. President and Fellows of Harvard College and Students for Fair Admissions, Inc. v. University of North Carolina, et al. has changed the landscape in higher education admissions processes by declaring affirmative action unlawful. It is imperative that those working in higher education admissions understand the ruling and implement contemporary best practices. Institutions of higher education who wish to promote student diversity are tasked with developing alternative strategies to affirmative action and must steer clear from using race as a determinant factor in admissions decisions. Aiming to identify diversity in individuals' lived experiences, focusing on recruitment efforts that organically lead to diverse applicants, adopting holistic, mission-driven admissions processes, and enhancing robust retention efforts may be effective means of fostering student diversity.
Variation in proliferative and cell cycle markers in Barrett’s esophagus in relation to circumferential and axial location in the esophagus
Authors: Umar Nosheen , Alleyne Lance , Cheung Danny , Rees James , Trudgill Caitlin , Zanetto Ulises , Muzaffar Suhail , Trudgill Nigel
Published: January 2024

Background

Adenocarcinoma in Barrett’s esophagus (BE) occurs more frequently between 12 and 3 o’clock at the gastroesophageal junction (GEJ).

Methods

BE patients were prospectively recruited from December 2013 to July 2016. Expression of p53, Ki-67, cyclin-D1, COX-2 and p21 was assessed in quadrantic biopsies from the proximal and distal margins of the BE segments. Cell cycle marker association with current or subsequent dysplasia or adenocarcinoma was examined.

Results

110 patients: median age 64 (IQR, 56–71) years; median BE segment length C4M6; and a median follow-up of 4.7 (IQR, 3.6–5.7) years. In total 13 (11.8%) had evidence of dysplasia or neoplasia (2.7% indefinite for dysplasia, 5.5% low grade, 1.8% high grade and 1.8% adenocarcinoma) at index endoscopy. Six (7%) developed dysplasia or neoplasia (1 low grade, 2 high grade and 3 adenocarcinoma) during follow-up. Ki-67 expression was highest at 3 o’clock, and overall was 49.6% higher in the 12-6 o’clock position compared to 6-12 o’clock [odds ratio (OR), 1.42 (95% confidence interval (CI), 1.00–2.12)]. A similar pattern was found with p21 [1.82 (1.00–3.47)]. There was increased expression of several markers in distal BE biopsies; cyclin-D1 [1.74 (1.29–2.34)]; Cyclo-oxygenase 2 [2.03 (1.48–2.78]) and p21 [2.06 (1.16–3.68)]. Expression of Ki-67 was lower in distal compared to proximal biopsies [0.58 (0.43–0.78)]. P53 expression had high specificity (93.8%) for subsequent low-grade dysplasia, high-grade dysplasia or adenocarcinoma.

Conclusion

Increased cellular proliferation was seen at 12-6 o’clock at the GEJ. Cell-cycle marker expression was increased at the GEJ compared to the proximal BE segment. These findings mirror reflux esophagitis and suggest ongoing reflux contributes to the progression of dysplasia and malignancy in BE.
The prevalence of fibromyalgia in adults at Al-Karak Jordan: a cross-sectional study
Authors: Akel Alaa , Sarhan Mohammed Y. , Dwairy Majed Al , Al-zu’bi Belal , Al-Qudah Ala , Alsmarat Omar A. , Alsaraireh Taif , Abu-Jeyyab Mohammad
Published: January 2024

Introduction:

Fibromyalgia is a chronic and intricate musculoskeletal disorder characterized by widespread pain, fatigue, and tenderness in specific anatomical regions. Although its prevalence varies among populations, understanding the prevalence in different geographical areas is crucial for healthcare planning. This cross-sectional study aims to determine the prevalence of fibromyalgia in adults residing in Al-Karak, Jordan. The city’s unique demographic and environmental characteristics may influence the occurrence of fibromyalgia among its adult population. The study aims to address gaps in knowledge, provide localized insights, and shed light on fibromyalgia’s burden on the community’s health. Accurate prevalence data aids healthcare planning and resource allocation.

Methods:

This research collected data from 965 social media participants using Google Forms. The American College of Rheumatology survey criteria for diagnosing fibromyalgia were used. To investigate the predictive value of various parameters, univariate and multivariate logistic regression analyses were performed.

Results:

The study found a 26.5% prevalence of fibromyalgia in the studied population. Female gender, mental health illnesses, and comorbidities like irritable bowel syndrome, psychiatric disorders, and rheumatological and neurological diseases were significantly associated with fibromyalgia. Age, BMI, marital status, employment status, and certain comorbidities did not show statistically significant predictive value.

Conclusion:

This study sheds light on fibromyalgia’s prevalence and associated factors in the Al-Karak population. The identified predictors highlight the necessity for comprehensive healthcare strategies and interventions to mitigate the disease burden. These findings aid policymakers and healthcare professionals in planning and implementing effective measures for fibromyalgia management and prevention. Further research is warranted to deepen our understanding of fibromyalgia’s complexity and its implications in this region.
Race and Ethnic Group Enrollment and Outcomes for Wilms Tumor: Analysis of the Current Era Children’s Oncology Group Study, AREN03B2
Authors: Lovvorn Harold N , Renfro Lindsay A , Benedetti Daniel J , Kotagal Meera , Phelps Hannah M , Ehrlich Peter F , Lo Andrea C , Sandberg Jesse K , Treece Amanda L , Gow Kenneth W , Glick Richard D , Davidoff Andrew M , Cost Nicholas G , Dix David B , Fernandez Conrad V , Dome Jeffrey S , Geller James I , Mullen Elizabeth A
Published: January 2024

BACKGROUND:

To review race and ethnic group enrollment and outcomes for Wilms tumor (WT) across all 4 risk-assigned therapeutic trials from the current era Children’s Oncology Group Renal Tumor Biology and Risk Stratification Protocol, AREN03B2.

STUDY DESIGN:

For patients with WT enrolled in AREN03B2 (2006 to 2019), disease and biologic features, therapeutic study-specific enrollment, and event-free (EFS) and overall (OS) 4-year survival were compared between institutionally reported race and ethnic groups.

RESULTS:

Among 5,146 patients with WT, no statistically significant differences were detected between race and ethnic groups regarding subsequent risk-assigned therapeutic study enrollment, disease stage, histology, biologic factors, or overall EFS or OS, except the following variables: Black children were older and had larger tumors at enrollment, whereas Hispanic children had lower rates of diffuse anaplasia WT and loss of heterozygosity at 1p. The only significant difference in EFS or OS between race and ethnic groups was observed among the few children treated for diffuse anaplasia WT with regimen UH-1 and -2 on high-risk protocol, AREN0321. On this therapeutic arm only, Black children showed worse EFS (hazard ratio = 3.18) and OS (hazard ratio = 3.42). However, this finding was not replicated for patients treated with regimen UH-1 and -2 under AREN03B2 but not on AREN0321.

CONCLUSIONS:

Race and ethnic group enrollment appeared constant across AREN03B2 risk-assigned therapeutic trials. EFS and OS on these therapeutic trials when analyzed together were comparable regarding race and ethnicity. Black children may have experienced worse stage-specific survival when treated with regimen UH-1 and -2 on AREN0321, but this survival gap was not confirmed when analyzing additional high-risk AREN03B2 patients.
Whole genome sequencing and genotyping Klebsiella pneumoniae multi-drug resistant hospital isolates from Western Kenya
Authors: Dinda Victor , Kimang’a Andrew Nyerere , Kariuki Daniel , Sifuna Anthony Wawire , O’Brien Thomas James , Welch Martin , Reva Oleg N.
Published: January 2024

Objectives.

Klebsiella pneumoniae

are a frequent cause of nosocomial infections worldwide. Sequence type 147 (ST147) has been reported as a major circulating high-risk lineage in many countries, and appears to be a formidable platform for the dissemination of antimicrobial resistance (AMR) determinants. However, the distribution of this pathogen in Western African hospitals has been scarcely studied. The main objective of this work was to perform whole genome sequencing of

K. pneumoniae

isolates from a referral hospital in Kakamega (Kenya) for genotyping and identification of AMR and virulence determinants.

Methods. In total, 15

K

.

pneumoniae

isolates showing a broad spectrum antimicrobial resistance were selected for whole genome sequencing by Illumina HiSeq 2500 platform.

Results. ST147 was the dominant lineage among the highly-resistant

K. pneumoniae

isolates that we sequenced. ST147 was associated with both community- and the hospital-acquired infections, and with different infection sites, whereas other STs were predominantly uropathogens. Multiple antibiotic resistance and virulence determinants were detected in the genomes including extended-spectrum β-lactamases (ESBL) and carbapenemases. Many of these genes were plasmid-borne.

Conclusions. Our data suggest that the evolutionary success of ST147 may be linked with the acquisition of broad host-range plasmids, and their propensity to accrue AMR and virulence determinants. Although ST147 is a dominant lineage in many countries worldwide, it has not been previously reported as prevalent in Africa. Our data suggest an influx of new nosocomial pathogens with new virulence genes into African hospitals from other continents.
PARP1 condensates differentially partition DNA repair proteins and enhance DNA ligation
Authors: Sang Christopher Chin , Moore Gaelen , Tereshchenko Maria , Nosella Michael L. , Zhang Hongshan , Alderson T. Reid , Dasovich Morgan , Leung Anthony , Finkelstein Ilya J. , Forman-Kay Julie D. , Lee Hyun O.
Published: January 2024

Poly(ADP-ribose) polymerase 1 (PARP1) is one of the first responders to DNA damage and plays crucial roles in recruiting DNA repair proteins through its activity – poly(ADP-ribosyl)ation (PARylation). The enrichment of DNA repair proteins at sites of DNA damage has been described as the formation of a biomolecular condensate. However, it is not understood how PARP1 and PARylation contribute to the formation and organization of DNA repair condensates. Using recombinant human PARP1in vitro, we find that PARP1 readily forms viscous biomolecular condensates in a DNA-dependent manner and that this depends on its three zinc finger (ZnF) domains. PARylation enhances PARP1 condensation in a PAR chain-length dependent manner and increases the internal dynamics of PARP1 condensates. DNA and single-strand break repair proteins XRCC1, LigIII, Polβ, and FUS partition in PARP1 condensates, although in different patterns. While Polβ and FUS are both homogeneously mixed within PARP1 condensates, FUS enrichment is greatly enhanced upon PARylation whereas Polβ partitioning is not. XRCC1 and LigIII display an inhomogeneous organization within PARP1 condensates; their enrichment in these multiphase condensates is enhanced by PARylation. Functionally, PARP1 condensates concentrate short DNA fragments and facilitate compaction of long DNA and bridge DNA ends. Furthermore, the presence of PARP1 condensates significantly promotes DNA ligation upon PARylation. These findings provide insight into how PARP1 condensation and PARylation regulate the assembly and biochemical activities in DNA repair foci, which may inform on how PARPs function in other PAR-driven condensates.
Molecular charmed baryons and pentaquarks from light-meson exchange saturation
Authors: Yan Mao-Jun , Peng Fang-Zheng , Pavon Valderrama Manuel
Published: January 2024

The spectrum of the cqq baryons contains a few states whose nature is not clearly a three-quark composite and which might have a sizable baryon-meson component. Examples include the Σc(2800) or the Λc(2940). Here we explore the spectrum of two-body systems composed of a light, octet baryon and a charmed meson (or antimeson) within a simple contact-range theory in which the couplings are saturated by light-meson exchanges. This results in the prediction of a series of composite anticharmed pentaquarks (c¯qqqq) and singly charmed baryons (cq¯qqq). Among the latter we find J=12 ΞD and J=32 ΞD* bound states with masses matching those of the recently observed Ωc(3185) and Ωc(3327) baryons.

Published by the American Physical Society
2024
Probing inelastic dark matter at the LHC, FASER, and STCF
Authors: Lu Chih-Ting , Tu Jianfeng , Wu Lei
Published: January 2024

In this work, we explore the potential of probing the inelastic dark matter (DM) model with an extra U(1)D gauge symmetry at the Large Hadron Collider, Forward Search Experiment, and Super Tau Charm Factory. To saturate the observed DM relic density, the mass splitting between two light dark states has to be small enough and thus leads to some distinctive signatures at these colliders. By searching for the long-lived particle, the displaced muon jets, the soft leptons, and the monophoton events, we find that the inelastic DM mass in the range of 1 MeV to 210 GeV could be tested.

Published by the American Physical Society
2024
Exploring the performance impact of unit load selection in order picking: evidence from a cold retail supply chain
Authors: Loske Dominic , Modica Tiziana , Klumpp Matthias , Montemanni Roberto
Published: January 2024

Purpose

Prior literature has widely established that the design of storage locations impacts order picking task performance. The purpose of this study is to investigate the performance impact of unit loads, e.g. pallets or rolling cages, utilized by pickers to pack products after picking them from storage locations.

Design/methodology/approach

An empirical analysis of archival data on a manual order picking system for deep-freeze products was performed in cooperation with a German brick-and-mortar retailer. The dataset comprises N = 343,259 storage location visits from 17 order pickers. The analysis was also supported by the development and the results of a batch assignment model that takes unit load selection into account.

Findings

The analysis reveals that unit load selection affects order picking task performance. Standardized rolling cages can decrease processing time by up to 8.42% compared to standardized isolated rolling boxes used in cold retail supply chains. Potential cost savings originating from optimal batch assignment range from 1.03% to 39.29%, depending on batch characteristics.

Originality/value

This study contributes to the literature on factors impacting order picking task performance, considering the characteristics of unit loads where products are packed on after they have been picked from the storage locations. In addition, it provides potential task performance improvements in cold retail supply chains.
How knowledge-based HRM practices and market turbulence foster organizational innovation capability: a two-path mediating role of knowledge sharing
Authors: Le Phong Ba , Son Than Thanh
Published: January 2024

Purpose

The purpose of this paper is to investigate the mediating roles of tacit and explicit knowledge sharing (KS) in linking the relationship between knowledge-based HRM practices and innovation competence of firms. This study also explores the potential moderating role of market turbulence in fostering the influence of KS behaviors on two forms of innovation competence namely radical innovation and incremental innovation.

Design/methodology/approach

The paper applied the quantitative approach and structural equation modeling to examine the correlation among the latent constructs based on the survey data collected from 293 participants in 115 firms.

Findings

The empirical findings of this study support the mediating role of KS behaviors in the relationship between knowledge-based HRM practices and aspects of innovation competence. It highlights the important role of market turbulence in stimulating the influence of KS behaviors on innovation capabilities.

Research limitations/implications

Future research should investigate the impact of knowledge-based HRM practices on innovation capability via the mediating effects of knowledge management processes to bring better understanding of the importance of knowledge resources in organizations.

Originality/value

The paper significantly contributes to increasing knowledge and insights into the antecedent role of knowledge-based HRM practices, the mediating role of KS behaviors as well as the moderating role of market turbulence in fostering radical and incremental innovation, thereby advancing the body of comprehension of knowledge-based resources and innovation theory.
Mental health in selected MENA countries during COVID-19: an empirical investigation
Authors: Fikry Pakinam Mahmoud
Published: January 2024

Purpose

The outbreak of COVID-19 not only had serious negative impacts on the world economy but also on the global mental health because of the psychological disorders associated with the spread of the pandemic, the increased degree of uncertainty and the unprecedented measures taken by different countries to face the pandemic’s spread. This paper analyses the mental health well-being of individuals in selected MENA countries (Jordan, Morocco, Tunisia and Egypt) during the pandemic.

Design/methodology/approach

The study employs a pooled OLS model using the Economic Research Forum (ERF) COVID-19 MENA Monitor Survey panel dataset collected during 2020 and 2021.

Findings

The findings show that there is no association between the mental health of individuals in the selected countries and their age, gender, family size, marital status, receipt of social support and participation in care work. Mental health improved at higher levels of education, being employed, being a rural area resident and living in Morocco or Tunisia compared to living in Jordan while it worsened as income declined, food insecurity and anxiety about being infected with Covid-19 increased, being a resident in camps, and during waves 4 and 5. Based on these results, it is recommended that suitable financial, physical and human resources should be directed towards the provision of mental health care services in the region. Also, mental health care services should be accessible to different population groups, with a special focus towards the most vulnerable since they are more prone to mental illnesses, especially during health crises and economic shocks. This should be accompanied by increasing awareness about the provided services and reducing stigma against mental illnesses. Furthermore, introduction of policies targeted towards reducing food insecurity and income instability can play a key role in enhancing mental well-being.

Originality/value

Although few papers have previously investigated the impact of COVID-19 on mental health in MENA countries, most of them have focused on a country-level analysis and adopted a gender perspective. Hence, this paper aims at exploring the association between mental health well-being and socio-economic factors in selected MENA countries during the pandemic.