bluuebunny/crossref_metadata_2025 huggingface dataset:
Corporate social responsibility, business strategy and governance performance
Authors: Elmassri Moataz , Kuzey Cemil , Uyar Ali , Karaman Abdullah S.
Published: July 2023

Purpose

This study aims to examine the effect of corporate social responsibility (CSR) adoption on differentiation and cost leadership strategies and how governance structure moderates this CSR–strategy relationship.

Design/methodology/approach

The study data were retrieved from Thomson Reuters for non-financial firms between 2013 and 2019, and a fixed-effects panel regression analysis was executed.

Findings

The results indicate that CSR fosters cost leadership strategy but weakens differentiation strategy. This result supports the value generation school for cost leaders but also confirms the agency theory perspective for differentiators. Moreover, the governance structure does not moderate the relationship between a firm's CSR engagement and its business strategy, which implies a lack of corporate policies that concurrently consider both its CSR investment and strategies.

Research limitations/implications

The findings of this study imply that cost leaders can integrate CSR practices into their business strategy and use their CSR engagement to increase their competitive position by stimulating cost efficiency and creating greater turnover. On the contrary, for differentiators, there is a trade-off between environmental and social engagement and business strategies. Thus, they are advised to enrich their unique product development abilities through the integration of environmental and social practices and reinforce their competitive position by addressing stakeholders' interests. The practical implication of the moderation analysis is that there is no rooted corporate policy behind the connection between CSR and firm strategy for both cost leaders and differentiators, which constitutes a missing link.

Originality/value

The findings of this study are of critical importance for firms, offering justification for the integration of two vital perspectives: social and environmental sustainability and financial sustainability. The moderating effect of governance performance tests the upper echelon's role in maintaining both sustainability perspectives concurrently and strengthening the legitimacy of the firms in society. Although maintaining a business strategy is important for shareholders' interests, pursuing a social and environmental sustainability strategy is crucial for meeting the expectations of all stakeholders.
Proposal of nursing diagnosis “adult disuse syndrome”: A conceptual derivation and integrative review
Authors: Ardila Suárez Edinson Fabian , Escalada‐Hernández Paula
Published: July 2023

Purpose

To develop a nursing diagnosis proposal derived from the concept of “disuse syndrome” based on an integrative review.

Methods

The conceptual derivation technique, proposed by Walker and Avant, was used in the following phases: an integrative review of the literature was carried out, applying the parameters of Whitermore and Knalf, where 43 articles were selected that covered the existence of the concept in the nursing discipline and other health sciences, the concepts were subsequently analyzed, and the new concept was redefined following the middle‐range theory of causality and validation of nursing diagnoses proposed by Oliveira‐Lopes et al.

Findings

The proposal of the new nursing diagnosis was developed, including the following elements: diagnostic label adult disuse syndrome, the corresponding definition, 25 defining characteristics, eight related factors, eight risk populations, and 14 associated problems.

Conclusions

The concept of the proposed new diagnosis describes adult disuse syndrome as a phenomenon that transcends the physiological component and should be viewed from a multidimensional view, expressing a clinical judgment related to a series of nursing diagnoses that appear together.

Implications for nursing practice

The results of this study will help nursing professionals to identify the phenomenon of adult disuse syndrome in any setting and in turn guide optimal care interventions that decrease the consequences of adult disuse syndrome.
Comorbid alcohol use disorder and posttraumatic stress disorder: A proof‐of‐concept randomized placebo‐controlled trial of buprenorphine and naltrexone combination treatment
Authors: Davis Lori L. , Petrakis Ismene L. , Pilkinton Patricia D. , Nolen Tracy , Vandergrift Nathan , Hirsch Shawn , Norrholm Seth D. , Kosten Thomas R.
Published: July 2023

Background

Effective pharmacologic treatments for comorbid alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are lacking. Kappa (κ) opioid receptor antagonists may address this unmet need. Buprenorphine is a κ‐opioid antagonist and a partial agonist of mu (μ) opioid receptors. Whereas naltrexone blocks all μ‐mediated effects combining it with buprenorphine yields a pharmacologic net effect of opioid receptor antagonism. Because no κ‐opioid receptor antagonist it available for clinical use, we tested this combination in a proof‐of‐concept study.

Methods

Consenting participants were enrolled in a Phase II, multisite, double‐blind, randomized, placebo‐controlled trial evaluating the effectiveness of sublingual (SL) buprenorphine combined with extended‐release (XR) injectable naltrexone for the treatment of comorbid AUD and PTSD. Eligible participants (n = 75) were randomized (1:1:1) to receive either buprenorphine 2 mg/day plus naltrexone‐XR (n = 35), buprenorphine 8 mg/day plus naltrexone‐XR (n = 6) or SL plus injectable placebo (n = 34) for 12 weeks. The buprenorphine 8 mg/day plus naltrexone‐XR arm was dropped early in the trial due to the negative impact of COVID‐19 on enrollment. A binary primary outcome of response at week 8 was defined as a decrease from baseline of ≥10 points on the past week Clinician‐Administered PTSD Scale (CAPS‐5) and a reduction of ≥1 of past month alcohol risk level, as defined by the World Health Organization (WHO) and measured by the Timeline Follow‐Back.

Results

Based on the results of a futility analysis, enrollment was stopped prior to reaching the initial goal of 90 participants. At the week eight primary timepoint, there were no statistically significant differences between buprenorphine plus naltrexone‐XR and placebo group for the primary composite outcome (OR = 0.63; p‐value = 0.52), or the subcomponents of the PTSD outcome (OR = 0.76; p‐value = 0.69) and AUD outcome (OR = 0.17; p‐value = 0.08). The placebo arm had a significantly higher proportion of participants with ≥1 WHO risk level reduction than the buprenorphine plus naltrexone‐XR arm (OR = 0.18, p value = 0.02).

Conclusions

This is the first study to evaluate the potential of κ‐opioid receptor antagonism for the treatment of comorbid AUD and PTSD. The combination of buprenorphine and naltrexone‐XR showed no significant improvement over placebo for the composite, PTSD, or alcohol measures.
Targeting PI3Kα increases the efficacy of anti‐PD‐1 antibody in cervical cancer
Authors: Jiang Wei , Ouyang Xueyan , Li Chunyan , Long Yixiu , Chen Wei , Ji Zhaodong , Shen Xuxia , Xiang Libing , Yang Huijuan
Published: July 2023

Targeting programmed death 1(PD‐1) has been approved for relapsed cervical cancer with unsatisfactory clinical efficacy. This study aims to analyse the impact of PI3K pathway activation on tumour immune microenvironment and evaluates the immune sensitization effect by PI3K inhibition in cervical cancer. The effect of PIK3CA mutation on PD‐L1 expression and CD8+ T cells differentiation was determined in cervical cancer tissues. Luciferase and ChIP‐qPCR/PCR assays were used to determine the transcriptional regulation of PD‐L1 by PIK3CA‐E545K. The effects of PI3K inhibitor treatment on immune environment in vitro and in vivo were evaluated by RNA sequencing (RNA‐seq) and flow cytometry. The efficacy of PI3K inhibitor and anti‐PD‐1 therapy was assessed in cell‐derived xenografts (CDX) and patients‐derived xenografts (PDX). PD‐L1 overexpression is more frequently observed in elder women with squamous cervical carcinoma. It predicts longer progress‐free survival and overall survival. PIK3CA mutation results in increased mRNA and protein levels of PD‐L1, the repression of CD8+ T cell differentiation in cervical cancer. Here, we report a case that continuous pembrolizumab monotherapy treatment induced complete remission of a recurrent cervical cancer patient with systemic metastasis and PIK3CA‐E545K mutation, implying that PIK3CA mutation is potentially a biomarker for pembrolizumab treatment in cervical cancer. Specifically, this mutation promotes the expression of PD‐L1 by upregulating the transcription factor IRF1. PI3Kα‐specific inhibitor markedly activates immune microenvironment by regulating the PD‐1/L1‐related pathways and promoting CD8+ T cell differentiation and proliferation in Caski‐CDXs with PIK3CA‐E545K mutation. PI3Kα inhibitor significantly enhances the anti‐tumour efficacy of PD‐1 blockade in CDXs and PDXs. PIK3CA mutations may predict the response of cervical cancer to PD‐1 blockade. The efficacy of PI3Kα inhibitors combined with PD‐1 antibodies is promising in cervical cancer and warrants additional clinical and mechanistic investigations.
Trans‐2,3‐enoyl‐CoA reductase‐like‐related catecholaminergic polymorphic ventricular tachycardia with regular ventricular tachycardia and response to flecainide
Authors: Ebrahim Mohammad A. , Alkhabbaz Ali A. , Albash Buthaina , AlSayegh Ali H. , Webster Gregory
Published: July 2023

Introduction

We describe a unique case of TECRL‐CPVT presented with cardiac arrest.

Methods

Post resuscitation, the patient developed regular ventricular tachycardia featuring a left purkinje system morphology.

Results

There was clear suppression of arrhythmia with the addition of flecainide and isolated ventricular ectopy causing secondary T‐wave changes.

Conclusion

A high index of suspicion was required to eventually make the diagnosis through whole exome sequencing.
Living, quiescent Lactobacillus plantarum Lp90 probiotic, delivered topically to full thickness tissues in vitro via a just‐add‐water cream delivery system, stimulates the expression of elastin protein
Authors: Gruber James V. , Holtz Robert
Published: July 2023

Introduction

Delivering living probiotics to the skin can be challenging as most water‐containing cosmetic products require preservatives to maintain product stability. A recently introduced powdered technology [Stratabiosys™, Vantage Personal Care] allows for quiescent probiotic powders to be stored for extended periods of time. The powders can then be reconstituted to creams at the point of use by adding water and mixing and were examined in vitro on reconstructed human full thickness tissues to see if the probiotic had any influence of several important biomolecules expressed in the skin.

Materials and Methods

A probiotic powder containing 200 M CFU/gram of living quiescent Lactobacillus plantarum Lp90 was reconstituted to a cream by adding ultrapure water and gently mixing the components at room temperature to quickly produce a cream. The resulting cream was tested topically on Epiderm® Full Thickness Tissues by treating the tissues for 24 h, removing the cream with a PBS rinse and then repeating the treatment for another 24 h. The resulting tissues were examined for four strategically important skin biomolecules including Type 1A collagen, elastin, filaggrin and hyaluronic acid. The probiotic‐containing powder was tested against untreated tissues and powders not containing probiotics and powders containing measured amounts of one of two cryoprotectants known to be used to maintain the integrity of the quiescent probiotics during drying of the quiescent probiotic powders.

Results

It was found that topical treatment on Epiderm® tissues with creams containing 2 M (1%), 4 M (2%) and 6 M (3%) CFU/gram prepared from a base powder containing 200 M CFU/gram of Lactobacillus plantarum Lp90 stimulated elastin expression in a dose dependent fashion. There was no effect on the other biomolecules examined in the studies. In addition, it was found that creams made from powders containing only the known cryoprotectants, not bacteria, had no influence on elastin expression.

Conclusion

The results of this study demonstrate that topical delivery of probiotics is possible from powders containing quiescent probiotic powders converted to creams just prior to application to the tissues. In the case of a powder containing Lactobacillus plantarum Lp90, topical application significantly increased expression of elastin in the skin replicants after 48 h of exposure to the cream made with the probiotic. The elastin‐stimulating effects are not coming from the oligosaccharide cryoprotectants used to maintain the probiotic powders in their quiescent, dried state. The results indicate that it is the living Lactobacillus plantarum probiotic that is stimulating the elastin expression in the skin tissues.
Pharmacokinetics and tolerability of multiple‐day oral dosing of mycophenolate mofetil in healthy horses
Authors: Bello Kaitlyn , Lorch Gwendolen , Kim Kyeongmin , Toribio Ramiro E. , Yan Liwei , Xie Zhiliang , Hill Kasey , Phelps Mitch
Published: July 2023

Background

Additional efficacious immunomodulatory treatment is needed for the management of immune‐mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses.

Hypothesis/Objectives

To evaluate the pharmacokinetics (PK) of multiple‐day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen.

Animals

Six healthy Standardbred mares.

Methods

Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough samples collected every 24 hours, immediately before morning drug administration. Noncompartmental PK analyses were performed to determine primary PK parameters, followed by calculation of geometric means and coefficients of variation. A CBC, serum biochemical profile, physical examination, and fecal scoring were used to assess dose tolerability.

Results

Seven days of treatment resulted in a mycophenolic acid (MPA) area under the curve (AUC0‐12) of 12 594 h × ng/mL (8567‐19 488 h × ng/mL) and terminal half‐life (T1/2) of 11.3 hours (7.5‐15.9 hours), yielding minor metabolite accumulation in all horses treated. Salmonellosis was detected in the feces of 2 horses by Day 7, and all horses developed myelosuppression, hyperbilirubinemia, hyporexia, decreased gastrointestinal motility, and decreased fecal output by the seventh day of treatment.

Conclusion and Clinical Importance

Administration of MMF at 10 mg/kg PO q12h resulted in hematologic and clinical toxicity within 1 week of treatment. A decreased MMF dose, frequency, or both is needed to avoid colic. Drug monitoring should include frequent hemograms, serum biochemical profiles, and strict biosecurity protocols.
Evidence that OLE RNA is a component of a major stress‐responsive ribonucleoprotein particle in extremophilic bacteria
Authors: Breaker Ronald R. , Harris Kimberly A. , Lyon Seth E. , Wencker Freya D. R. , Fernando Chrishan M.
Published: July 2023

OLE RNA is a ~600‐nucleotide noncoding RNA present in many Gram‐positive bacteria that thrive mostly in extreme environments, including elevated temperature, salt, and pH conditions. The precise biochemical functions of this highly conserved RNA remain unknown, but it forms a ribonucleoprotein (RNP) complex that localizes to cell membranes. Genetic disruption of the RNA or its essential protein partners causes reduced cell growth under various stress conditions. These phenotypes include sensitivity to short‐chain alcohols, cold intolerance, reduced growth on sub‐optimal carbon sources, and intolerance of even modest concentrations of Mg2+. Thus, many bacterial species appear to employ OLE RNA as a component of an intricate RNP apparatus to monitor fundamental cellular processes and make physiological and metabolic adaptations. Herein we hypothesize that the OLE RNP complex is functionally equivalent to the eukaryotic TOR complexes, which integrate signals from various diverse pathways to coordinate processes central to cell growth, replication, and survival.
Electrochemical waste-heat harvesting
Authors: Yu Boyang , Duan Jiangjiang
Published: July 2023

A combined thermal and electrochemical device enhances voltage and hydrogen production
Innovate beyond PFAS
Authors: Scheringer Martin
Published: July 2023

New proposed legislation on “forever” chemicals is under consideration in Europe and the United States, where per- and polyfluoroalkyl substances (PFAS) are a hot topic for regulators and lawmakers. On both sides of the Atlantic, regulation of widely used PFAS has been complex and evolving. Their presence in hundreds of different products—from nonstick cookware to food packaging to firefighting foam—and their persistence in food, drinking water, and the environment have resulted in a pollution problem of unprecedented scale. Recently, for example, it was reported that 45% of the tap water in the United States contains at least one type of PFAS. Because these compounds are so chemically stable that they do not degrade in the environment (including in the human body), PFAS seriously challenge long-established ideas of how chemicals can be used, assessed, and regulated, and it remains to be seen whether the new regulations will solve this problem.
Burden of blindness and vision loss in China over the past 30 years: findings and predictions based on the Global Burden of Disease Study 2019
Authors: Jiang Bo , Yao Qingying , Yuan Xianbin , Liu Gaoqin , Lu Peirong
Published: July 2023

Aims

To investigate the burden of blindness and vision loss (BVL) in China over the past 30 years according to year, age and sex, and to estimate future predictions.

Methods

We analysed the years lived with disability (YLDs), number of cases, age-standardised YLD rates (ASYRs) and age-standardised prevalence rates (ASPRs) of BVL in China from 1990 to 2019. We focused on changes over time using estimated annual percentage changes (EAPCs). Additionally, we used the Bayesian age-period-cohort model to predict the BVL burden from 2020 to 2030.

Results

The number of YLDs and prevalent cases due to BVL increased from 2.57 (95% uncertainty interval (UI) 1.74 to 3.72) and 90.76 million (95% UI 72.21 to 111.92) in 1990 to 5.42 (95% UI 3.61 to 8.02) and 211.67 million (95% UI 168.21 to 259.66) in 2019, respectively. The BVL ASYRs and ASPRs showed a decreasing trend, with EAPCs of −0.13 (95% CI −0.28 to 0.02) and −0.11 (95% CI −0.19 to −0.04), respectively. The elderly and female populations had a higher BVL burden. The numbers of YLDs and cases due to BVL are projected to continue rising to 7.74 and 279.49 million in 2030, respectively. The ASYRs and ASPRs also showed increasing trends.

Conclusion

While rates of BVL in China have decreased, there has been a notable increase in the number of YLDs and new cases over the past 30 years. Projections suggest that the burden of BVL will continue to rise over the next 11 years. To address this challenge, appropriate policies must be implemented.
Lifelong differences in cancer incidence and mortality between subgroups of similar socioeconomic status in the Royal Norwegian Navy
Authors: Strand Leif Aage , Rudvin Inger , Martinsen Jan Ivar , Fadum Elin Anita , Grimsrud Tom K
Published: July 2023

Objectives

In a previous cohort study of 28 300 Navy servicemen, vessel crews showed higher cancer incidence and mortality than did land-based personnel. We have extended the follow-up to look for changes in cancer risk, and to explore temporal trends in cancer incidence and cancer mortality during more than six decades of follow-up.

Methods

Cancer incidence and total cancer mortality were compared with the general population by calculating standardised ratios (standardised incidence ratios (SIRs), standardised mortality ratios) for the entire follow-up, with temporal trends through seven consecutive 10-year time spans from individual entry to follow-up. Rates were compared between the subgroups using Poisson regression, expressed as rate ratios (RRs).

Results

Cancer incidence in Navy servicemen suggested a healthy soldier effect limited to the first three decades of follow-up and confined to land-based personnel. Overall, vessel crews showed 13% higher cancer incidence and 36% higher cancer mortality than other Navy servicemen. Some of the differences may be explained by a higher risk in vessel crews of cancers known to have less than 25% 5-year relative survival (RR=1.71), such as cancers of the lung, liver, pancreas and mesothelioma.

Conclusion

Through most of the observation time, vessel crews had an overall cancer SIR that was higher than that of land-based personnel. Much of this excess involved cancers with a generally poor prognosis, linked to lifestyle and work environment. The contrasts in cancer incidence and mortality between the two subgroups of Navy servicemen persisted through more than six decades.
Resonance Y-type soliton and hybrid solutions for a (2+1)-dimensional generalized Calogero-Bogoyavlenskii-Konopelchenko-Schiff system in a fluid or plasma
Authors: Zheng Lu , Tian Bo , Yang Dan-Yu , Chen Yu-Qi
Published: July 2023

In this paper, a (2+1)-dimensional generalized Calogero-Bogoyavlenskii-Konopelchenko-Schiff system in a fluid or plasma is investigated. Via the Hirota method and symbolic computation, we work out some two-resonance Y-type soliton solutions as well as some hybrid solutions composed of the two-resonance Y-type solitons and solitons/breathers. Graphically, we display some two-resonance Y-type solitons. We present the interactions between the two-resonance Y-type soliton and one soliton, among the two-resonance Y-type soliton and two solitons, between the two-resonance Y-type soliton and first-order breather as well as among the two-resonance Y-type soliton and second-order breathers.
Effect of torsional deformation on electronic structure and optical properties of silicon-doped WS2
Authors: Qian Shaoran , Liu Guili , Wei Lin , Zhao Jingwei , Zhang Guoying
Published: July 2023

In this paper, the structural, electrical and optical effects of WS2 doped with silicon atoms after torsional deformation are investigated using first-principles calculations. First-principles calculations for metal disulfide-WS2. The doping of Si atoms gives WS2 a tunable band gap, and the surface state is successfully transformed from a 2.0[Formula: see text]eV band gap to a quasi-metal with a 0.254[Formula: see text]eV band gap, and the change of the doped Si atoms causes a redshift in the absorption peak and a blueshift in the reflection peak. The band gap of WS2 can be effectively adjusted by torsional deformation on the basis of Si-doped atoms in the range 0.254–0.052[Formula: see text]eV. Calculations of optical properties show that Si-doped WS2 with a torsion angle of [Formula: see text] has the lowest light absorption peak and Si-doped WS2 with a torsion angle of [Formula: see text] has the lowest light reflection peak. This paper opens up new possibilities for designing materials on demand.
An Analytical Solution on Vibration Reduction and Shear Force Mitigation of Cantilever Mindlin Plates Using Orthogonal Ribs
Authors: Guo Hui , Zhang Kai , Lin Tian Ran
Published: July 2023

Vibration of aircraft wings and the dynamic stress concentration at the clamped edge are important research topics due to concerns on the safety of aircrafts. To have a better understanding of the problem, the free and forced vibration response of a ribbed rectangular cantilever plate representing a section of an aircraft wing is investigated in this study. A new analytical solution is developed for the vibration analysis of rib stiffened cantilever plates using Mindlin plate and Timoshenko beam theories alongside the finite integral transform technique. The one- and two-dimensional integral transforms are applied to the governing equations of beams and plates, respectively, where the coupling force components at the interface between the base plate and the beam(s) can be automatically defined during the integral transform. Eventually, the partial differential equations are transformed into a system of linear algebraic equations in which its derivation is rigorous and easily implemented. Good agreements are found between the results of analytical solution, finite element analysis (FEA) and related literature. The solution is then employed to study the vibration suppression of cantilever plates and the shear force at the clamped edge. It is found that the insertion of a pair of orthogonal ribs in the plate can effectively reduce its vibration. An optimum orthogonal ribbing pattern is obtained using multi-objective particle swarm optimization (MOPSO) algorithm, taking into consideration both the vibration suppression of the plate and the maximum induced shear force at the corners of the clamped edge.
FRACTIONAL ORDER MODEL FOR CARDIOVASCULAR SYSTEM USING HEURISTIC OPTIMIZATION APPROACH
Authors: RESMI V. L. , SELVAGANESAN N.
Published: July 2023

Cardiovascular diseases like atherosclerosis, peripheral arterial disease, coronary heart disease, etc. are dangerous and hence early detection of such diseases is important in the field of medical sciences. The existing methods used for diagnosing diseases are time-consuming and highly expensive. On the other hand, experimentation with Cardiovascular System (CVS) for the analysis and decision making for treatment is unsafe and hence it is important to develop an accurate CVS model. It is observed from the existing integer order cardiovascular models that the viscoelastic property of four chambers is not taken into consideration. To accommodate these properties, this paper proposes a fractional order model by introducing fractionality to the dynamical equation of CVS. Further, an optimization method is presented to obtain the fractionality of different chambers by minimizing the integral square error between clinical data of healthy human and model output using Cuckoo search, Firefly and Accelerated particle swarm algorithms. The results indicate that fractional models are better than integer order CVS models and specifically, the Firefly algorithm provides a better fractional model than the models obtained from other algorithms. Further, the best model obtained using firefly algorithm is considered for simulating the diseases (i) increased arterial stiffness and (ii) atherosclerosis.
Near-optimal Lower Bounds on Quantifier Depth and Weisfeiler–Leman Refinement Steps
Authors: Berkholz Christoph , Nordström Jakob
Published: July 2023

We prove near-optimal tradeoffs for quantifier depth (also called quantifier rank) versus number of variables in first-order logic by exhibiting pairs of
n
-element structures that can be distinguished by a
k
-variable first-order sentence but where every such sentence requires quantifier depth at least 
n

Ω (
k
/log
k
)

. Our tradeoffs also apply to first-order counting logic and, by the known connection to the
k
-dimensional Weisfeiler–Leman algorithm, imply near-optimal lower bounds on the number of refinement iterations.

A key component in our proof is the hardness condensation technique introduced by Razborov in the context of proof complexity. We apply this method to reduce the domain size of relational structures while maintaining the minimal quantifier depth needed to distinguish them in finite variable logics.
Interactive Effects of Guided Inquiry and Teachers’ Experience on Chemistry Students’ Interest
Authors: Igboanugo Benson Ikechukwu
Published: July 2023

The dwindling of students’ interest in chemistry which leads to students poor achievement in chemistry calls for an inward investigation on the interactive effects of two influential factors on pedagogy, effective mode of instruction and the teacher quality on students’ interest in chemistry. Thus, this study adopted the quasiexperimental design to investigate interactive effects of guided inquiry and teachers’ years of experience on students’ interest in chemistry. The study was conducted using Senior Secondary School 2 chemistry students in Ogidi Education zone of Anambra state, Nigeria. One research question and one hypothesis guided the study. 310 chemistry students random sampled in twelve public secondary schools and twelve regular teachers were included in the study. Data were collected using validated chemistry interest inventory (CII). The CII had an average reliability index of 0.93 as determined using Cronbach’s alpha reliability coefficient. The hypothesis was tested using the analysis of covariance (ANCOVA). The study revealed significant interactive effects of teachers’ years of experience and guided inquiry on students’ interest in chemistry.
Radiotherapy-Induced Neurocognitive Impairment Is Driven by Heightened Apoptotic Priming in Early Life and Prevented by Blocking BAX
Authors: Singh Rumani , Yu Stacey , Osman Marwa , Inde Zintis , Fraser Cameron , Cleveland Abigail H. , Almanzar Nicole , Lim Chuan Bian , Joshi Gaurav N. , Spetz Johan , Qin Xingping , Toprani Sneh M. , Nagel Zachary , Hocking Matthew C. , Cormack Robert A. , Yock Torunn I. , Miller Jeffrey W. , Yuan Zhi-Min , Gershon Timothy , Sarosiek Kristopher A.
Published: July 2023

Although external beam radiotherapy (xRT) is commonly used to treat central nervous system (CNS) tumors in patients of all ages, young children treated with xRT frequently experience life-altering and dose-limiting neurocognitive impairment (NI) while adults do not. The lack of understanding of mechanisms responsible for these differences has impeded the development of neuroprotective treatments. Using a newly developed mouse model of xRT-induced NI, we found that neurocognitive function is impaired by ionizing radiation in a dose- and age-dependent manner, with the youngest animals being most affected. Histologic analysis revealed xRT-driven neuronal degeneration and cell death in neurogenic brain regions in young animals but not adults. BH3 profiling showed that neural stem and progenitor cells, neurons, and astrocytes in young mice are highly primed for apoptosis, rendering them hypersensitive to genotoxic damage. Analysis of single-cell RNA sequencing data revealed that neural cell vulnerability stems from heightened expression of proapoptotic genes including BAX, which is associated with developmental and mitogenic signaling by MYC. xRT induced apoptosis in primed neural cells by triggering a p53- and PUMA-initiated, proapoptotic feedback loop requiring cleavage of BID and culminating in BAX oligomerization and caspase activation. Notably, loss of BAX protected against apoptosis induced by proapoptotic signaling in vitro and prevented xRT-induced apoptosis in neural cells in vivo as well as neurocognitive sequelae. On the basis of these findings, preventing xRT-induced apoptosis specifically in immature neural cells by blocking BAX, BIM, or BID via direct or upstream mechanisms is expected to ameliorate NI in pediatric patients with CNS tumor.

Significance:

Age- and differentiation-dependent apoptotic priming plays a pivotal role in driving radiotherapy-induced neurocognitive impairment and can be targeted for neuroprotection in pediatric patients.
Mutation Analysis of PKD1 and PKD2 Genes in a Large Italian Cohort Reveals Novel Pathogenic Variants Including a Novel Complex Rearrangement
Authors: Orisio Silvia , Noris Marina , Rigoldi Miriam , Bresin Elena , Perico Norberto , Trillini Matias , Donadelli Roberta , Perna Annalisa , Benigni Ariela , Remuzzi Giuseppe
Published: July 2023

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidney. It occurs in adulthood but is also rarely diagnosed in early childhood. The majority of the disease-causing variants observed in ADPKD patients are in two genes: PKD1 and PKD2. Methods: 237 patients from 198 families with a clinical diagnosis of ADPKD were screened for PKD1 and PKD2 genetic variants using Sanger sequencing and multiple ligation-dependent probe amplification analysis. Results: Disease-causing (diagnostic) variants were identified in 173 families (211 patients), 156 on PKD1 and 17 on PKD2. Variants of unknown significance were detected in 6 additional families, while no mutations were found in the remaining 19 families. Among the diagnostic variants detected, 51 were novel. In ten families, seven large rearrangements were found and the molecular breakpoints of 3 rearrangements were identified. Renal survival was significantly worse for PKD1-mutated patients, particularly those carrying truncating mutations. In patients with PKD1 truncating (PKD1-T) mutations, disease onset was significantly earlier than in patients with PKD1 non-truncating variants or PKD2-mutated patients. Conclusions: Comprehensive genetic testing confirms its utility in diagnosing patients with ADPKD and contributes to explaining the clinical heterogeneity observed in this disease. Moreover, the genotype-phenotype correlation can allow for a more accurate disease prognosis.
The Day-To-Day Practice of MMR and MSI Assessment in Colorectal Adenocarcinoma: What We Know and What We Still Need to Explore
Authors: Parente Paola , Grillo Federica , Vanoli Alessandro , Macciomei Maria Cristina , Ambrosio Maria Raffaella , Scibetta Nunzia , Filippi Emanuela , Cataldo Ivana , Baron Luigi , Ingravallo Giuseppe , Cazzato Gerardo , Melocchi Laura , Liserre Barbara , Giordano Carla , Arborea Graziana , Pilozzi Emanuela , Scapinello Antonio , Aquilano Maria Costanza , Gafà Roberta , Battista Serena , Dal Santo Luca , Campora Michela , Carbone Francesco Giuseppe , Sartori Chiara , Lazzi Stefano , Hanspeter Ester , Angerilli Valentina , Mastracci Luca , Fassan Matteo
Published: July 2023

Background: The DNA mismatch repair (MMR) system is a highly preserved protein complex recognizing short insertions, short deletions, and single base mismatches during DNA replication and recombination. MMR protein status is identified using immunohistochemistry. Deficit in one or more MMR proteins, configuring deficient MMR status (dMMR), leads to frameshift mutations particularly clustered in microsatellite repeats. Thus, microsatellite instability (MSI) is the epiphenomenon of dMMR. In colorectal cancer (CRC), MMR/MSI status is a biomarker with prognostic and predictive value of resistance to 5-fluorouracil and response to immune checkpoint inhibitor therapy. Summary: In this Review, we describe the challenges the practicing pathologist may face in relation to the assessment of MMR/MSI status and any open issues which still need to be addressed, focusing on pre-analytic issues, pitfalls in the interpretation, and technical aspects of the different assays. Key Messages: The current methods of detecting dMMR/MSI status have been optimized for CRCs, and whether these techniques can be applied to all tumor and specimen types is still not fully understood. Following the Food and Drug Administration (FDA), tissue/site agnostic drug approval of pembrolizumab for advanced/metastatic MSI tumors, MMR/MSI status in gastrointestinal tract is a common request from the oncologist. In this setting, several issues still need to be addressed, including criteria for sample adequacy.
Candidate Gene Expression in Regional Population and Its Relevance for Radiation Triage
Authors: Kannan Nandhini , Koshy Teena , Raavi Venkateswarlu , Bhaskar Emmanuel , Moorthy Swathy , Pulivadula Mohanarangam Venkata Sai , Srinivas Kondaveeti Satish , Visweswaran Shangamithra , Perumal Venkatachalam
Published: July 2023

Quantification of gene expression signatures has been substantiated as a potential and rapid marker for radiation triage and biodosimetry during nuclear emergencies. Similar to the established biodosimetry assays, the gene expression assay has drawbacks such as being highly dynamic and transient, not specific to ionizing radiation, and also influenced by confounding factors such as gender, health status, lifestyle, and inflammation. In view of that, prior knowledge of baseline expression of certain candidate genes in a population could complement the discrimination of the unexposed from the exposed individuals without the need for individual pre-exposure controls. We intended to establish a baseline expression of reported radiation-responsive genes such as CDKN1A, DDB2, FDXR, and PCNA in the blood samples of healthy human participants and then compare it with diabetic/hypertension participants (as a chronic inflammatory condition) drawn from south Indian population. Further, we have examined the appropriateness of the assay for radiation triage-like situations; i.e., the expression profiles of those genes were examined in the participants who underwent X-ray-based medical imaging. Acute inflammation induced by lipopolysaccharide exposure in the blood significantly increased the fold expression of those genes (p < 0.0001) compared to the control. Whereas the basal expression level of those genes among the participants with the inflammatory condition is marginally higher than those observed in the healthy participants; despite the excess, the fold increase in those genes between the groups did not differ significantly. Consistent with the inflammatory participants, the basal expression level of those genes in the blood sample of participants who received X-radiation during neuro-interventional and computed tomography imaging is marginally higher than those observed in the pre-exposure of respective groups. Nevertheless, the fold increase in those genes did not differ significantly as the fold change fell within the two folds. Thus, overall results suggest that the utility of CDKN1A, DDB2, FDXR, and PCNA gene expression for radiation triage specific after very low-dose radiation exposure needs to be interpreted with caution for a much more reliable triage.
Association of Self-Reported Nighttime Sleep Duration with Chronic Kidney Disease: China Health and Retirement Longitudinal Study
Authors: Jiang Bingxin , Tang Dongxu , Dai Neng , Huang Chen , Liu Yahang , Wang Ce , Peng Jiahuan , Qin Guoyou , Yu Yongfu , Chen Jiaohua
Published: July 2023

Introduction: The cohort study aimed to assess the association of nighttime sleep duration and the change in nighttime sleep duration with chronic kidney disease (CKD) and whether the association between nighttime sleep duration and CKD differed by daytime napping. Methods: This study included 11,677 individuals from the China Health and Retirement Longitudinal Study (CHARLS) and used data from the 2011 baseline survey and four follow-up waves. Nighttime sleep duration was divided into three groups: short (<7 h per night), optimal (7–9 h), and long nighttime sleep duration (>9 h). Daytime napping was divided into two groups: no nap and with a nap. We used Cox proportional hazards model to examine the effect of nighttime sleep duration at baseline and change in nighttime sleep duration on incident CKD and a joint effect of nighttime sleep duration and nap time on onset CKD. Results: With a follow-up of 7 years, the incidence of CKD among those with short, optimal, and long nighttime sleep duration was 9.89, 6.75, and 9.05 per 1,000 person-years, respectively. Compared to individuals with optimal nighttime sleep duration, short nighttime sleepers had a 44% higher risk of onset CKD (hazard ratio [HR]: 1.44, 95% confidence interval [CI]: 1.21–1.72). Compared to participants with persistent optimal nighttime sleep duration, those with persistent short or long nighttime sleep duration had an increased risk of incident CKD (HR: 1.44, 95% CI: 1.15–1.80). We found a lower incidence of CKD in participants with short nighttime sleep duration and a nap (HR: 0.74, 95% CI: 0.60–0.93), compared to those with short nighttime sleep duration and no nap. Conclusion: Short nighttime sleep duration and persistent long or short nighttime sleep duration were associated with a higher risk of onset CKD. Keeping persistent optimal nighttime sleep duration may help reduce CKD risk later in life. Daytime napping may be protective against CKD incidence.
Can Enhancement Pattern in Normal-Sized Optic Nerves on Magnetic Resonance Imaging Better Predict Tumor Invasion in Retinoblastoma Eyes?
Authors: Chiranthan Madhu , Meel Rachna , Sharma Sanjay , Lomi Neiwete , Kashyap Seema , Singh Bajaj Mandeep
Published: July 2023

Introduction: Optic nerve (ON) enhancement alone without ON thickening on contrast-enhanced magnetic resonance imaging (CE-MRI) can be associated with post-laminar optic nerve invasion (PLONI) in eyes with group E retinoblastoma. A few case reports and retrospective studies in the literature show a poor correlation between ON enhancement on MRI and ON invasion on histopathological examination (HPE). There is no universal consensus on the management of such cases. It is desirable that the presence and extent of a true ON invasion be reliably picked up before planning upfront enucleation in order to avoid stage II disease. Methods: In a prospective study conducted at a tertiary eye care center in North India, all retinoblastoma patients presenting with ON enhancement on imaging were evaluated. Demographic and imaging details, histopathological findings, and treatment details were recorded. The length and pattern of enhancement noted on MRI were correlated with histopathology. Follow-up was done till the end of the study period. Results: Six group E retinoblastoma eyes were evaluated. 3 eyes (50%) showed solid enhancement, 2 eyes (33.33%) had tram track pattern and 1 eye (16.66%) showed punctate enhancement pattern on CE-MRI. On histopathology, 5 (83.33%) cases showed PLONI and all 6 (100%) had ON head infiltration. The cut end of the ON was free in all cases. On correlating MRI and HPE, all eyes with solid enhancement pattern showed PLONI, of which 2/3 (66.6%) had diffuse ON infiltration. Only 50% of eyes with tram track patterns showed PLONI. The case which showed a punctate enhancement pattern showed focal infiltration by tumor cells with vacuolated cytoplasm on HPE. At the last follow-up, all patients were alive and free of disease. Conclusion: ON enhancement patterns may make it more predictive for PLONI on HPE. Solid enhancement pattern appears to correlate better with the extent of ON invasion on HPE, and longer lengths of solid ON enhancement may be considered for neoadjuvant chemotherapy rather than upfront enucleation.
Factors Associated with Hospital Readmission One Year Post-Discharge in Infants with Gastroschisis
Authors: Marquart John P. , Mukherjee Devashis , Canales Bethany N. , Flynn-O'Brien Katherine T. , Szabo Aniko , Wagner Amy J.
Published: July 2023

Introduction: Gastroschisis is the most common congenital abdominal wall defect with a rising prevalence. Infants with gastroschisis are at risk for multiple complications, leading to a potential increased risk for hospital readmission after discharge. We aimed to find the frequency and factors associated with an increased risk of readmission. Methods: A retrospective analysis of infants born with gastroschisis between 2013 and 2019 who received initial surgical intervention and follow-up care in the Children’s Wisconsin health system was performed. The primary outcome was the frequency of hospital readmission within 1 year of discharge. We also compared maternal and infant clinical and demographic variables between those readmitted for reasons related to gastroschisis, and those readmitted for other reasons or not readmitted. Results: Forty of 90 (44%) infants born with gastroschisis were readmitted within 1-year of the initial discharge date, with 33 (37%) of the 90 infants being readmitted due to reasons directly related to gastroschisis. The presence of a feeding tube (p < 0.0001), a central line at discharge (p = 0.007), complex gastroschisis (p = 0.045), conjugated hyperbilirubinemia (p = 0.035), and the number of operations during the initial hospitalization (p = 0.044) were associated with readmission. Maternal race/ethnicity was the only maternal variable associated with readmission, with Black race being less likely to be readmitted (p = 0.003). Those who were readmitted were also more likely to be seen in outpatient clinics and utilize emergency healthcare resources. There was no statistically significant difference in readmission based on socioeconomic factors (all p > 0.084). Conclusion: Infants with gastroschisis have a high hospital readmission rate, which is associated with a variety of risk factors including complex gastroschisis, multiple operations, and the presence of a feeding tube or central line at discharge. Improved awareness of these risk factors may help stratify patients in need of increased parental counseling and additional follow-up.
Prenatal and Neonatal Ultrasound and Magnetic Resonance Imaging Diagnosis of Sprengel’s Deformity with Unusual Associations
Authors: Jaczyńska Renata , Bekiesinska-Figatowska Monika , Sobieraj Paulina , Issat Tadeusz , Gos Monika , Obersztyn Ewa
Published: July 2023

Introduction: Sprengel’s deformity is a rare congenital anomaly of the shoulder rim. It is the most common congenital anomaly of the shoulder, associated with cosmetic deformity and abnormal shoulder function. Nonsurgical management can be considered for mild cases. Surgical intervention is indicated in moderate to severe cases with the goal of improving cosmetic appearance and function. The best surgical results are obtained in children aged 3–8 years. Correct diagnosis is very important because Sprengel’s deformity can be accompanied by additional abnormalities, even in mild cases, and lack of a diagnosis delays proper treatment of the child. The severity of the defect may progress, so it is important to correctly identify children with Sprengel’s deformity, even those with a mild form of the defect. Case Presentation: We report a case of prenatal sonographic diagnosis of Sprengel’s deformity with additional features, as yet undescribed and missed – although visible – on prenatal magnetic resonance imaging (MRI). Cesarean delivery was performed due to preterm rupture of membranes, and a postnatal MRI confirmed the unusual constellation of Sprengel’s anomaly with lateral meningocele, vestigial posterior meningocele, and lipoma tethering of the cord to the dural sac at the cervical-thoracic junction. Conclusion: Diagnosis of Sprengel’s deformity is possible with prenatal ultrasound. Asymmetry of the cervical spine, discontinuity of the vertebral arch and abnormal vertebral bodies, as well as the asymmetric position of the shoulder blades with the presence of an omovertebral bone are signs that can help diagnose the defect.
Selaginella subchaetoloma (Sect. Heterostachys; Selaginellaceae), a new species from Southwest China
Authors: FANG SHAO-LI , LI YU-XIN , ZHANG LI-BING , HE ZHAO-RONG , ZHOU XIN-MAO
Published: July 2023

A new lycophyte species, Selaginella subchaetoloma, is described. This species is relatively abundant in Southwest China. Materials of this species were previously identified as S. chaetoloma, but a detailed morphological study shows that the new species differs by plants with creeping sterile part and ascending fertile part and dorsal leaves with abruptly short-acuminate apex. Molecular phylogenetic results indicate that S. subchaetoloma and S. chaetoloma are not closely related.