bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of gastrointestinal landmarks using the gas‐sensing capsule and wireless motility capsule
Authors: Thwaites Phoebe A. , Yao Chu K. , Maggo Jasjot , John James , Chrimes Adam F. , Burgell Rebecca E. , Muir Jane G. , Parker Francis C. , So Daniel , Kalantar‐Zadeh Kourosh , Gearry Richard B. , Berean Kyle J. , Gibson Peter R.
Published: September 2022

Background

Accurate definition of the gastroduodenal and ileocaecal junctions (GDJ, ICJ) is essential for the measurement of regional transit times.

Aims

To compare the assessment of these landmarks using the novel gas‐sensing capsule and validated wireless motility capsule (WMC), and to evaluate intra‐subject variance in transit times

Methods

Healthy subjects ingested the gas‐sensing capsule and WMC tandemly in random order. Inter‐observer agreement was evaluated by intra‐class correlation coefficient (ICC). Agreement between the paired devices' transit times was assessed using Bland–Altman analysis; coefficient of variation was performed to express intra‐individual variance in transit times. Similar analyses were completed with tandemly ingested gas‐sensing capsules.

Results

The inter‐observer agreement for landmarks for both capsules was excellent (mean ICC ≥0.97) in 50 studies. The GDJ was identifiable in 92% of the gas‐sensing capsule studies versus 82% of the WMC studies (p = 0.27); the ICJ in 96% versus 84%, respectively (p = 0.11). In the primary cohort (n = 26), median regional transit times differed by less than 6 min between paired capsules. Bland–Altman revealed a bias of −0.12 (95% limits of agreement, −0.94 to 0.70) hours for GDJ and − 0.446 (−2.86 to 2.0) hours for ICJ. Similar results were found in a demographically distinct validation cohort (n = 24). For tandemly ingested gas‐sensing capsules, coefficients of variation of transit times were 11%–35%, which were similar to variance between the paired gas‐sensing capsule and WMC, as were the biases. The capsules were well tolerated.

Conclusions

Key anatomical landmarks are accurately identified with the gas‐sensing capsule in healthy individuals. Intra‐individual differences in transit times between capsules are probably due to physiological factors. Studies in populations with gastrointestinal diseases are now required.
Institutional cisnormativity and educational injustice: Trans children's experiences in primary and early secondary education in the UK
Authors: Horton Cal
Published: September 2022

Background

Transgender children are known to face a wide range of barriers, difficulties and injustices at school. Few studies have focused on the educational experiences of trans pupils who socially transition at or before primary school, with no such studies in the UK.

Aims

To learn about the at‐school experiences of transgender children who socially transitioned at or before primary school in the UK, listening to children's and parental accounts of navigating cisnormativity in UK primary and early secondary education.

Sample

The primary sample included 30 parents whose children had socially transitioned under the age of 11 in the UK. This sample was complemented with data directly from 10 of these trans children. The primary sample was accessed through six trans positive parenting groups in the UK, supplemented through snowball sampling.

Methods

Semi‐structured interviews produced a rich and detailed qualitative data set, that was analysed through inductive thematic analysis.

Results

Three major themes are presented, highlighting experiences of (i) institutional cisnormativity in UK schools, (ii) a failure to protect trans children and (iii) evidence of educational injustice. The results demonstrate how institutional cisnormativity leaves trans pupils in unsafe educational environments, contributing to school drop‐out and trauma.

Conclusions

Cisnormative attitudes normalize injustice, making it acceptable for trans children to lose access to education, or to experience trauma in school. Educators, schools and school leaders need to take action to protect trans children in our schools.
Retooling militancy: Labour revitalization and fixed‐duration strikes
Authors: Kallas John
Published: September 2022

Despite decades of decline in strike rates, recent scholarship has examined how unions and labour organizations are retooling the strike to confront increasing employer power. This study focuses on a militant labour union and the emergence of an understudied type of strike – the fixed‐duration strike – as a source of labour revitalization. Drawing from qualitative data gathered on fixed‐duration strikes organized by a union of registered nurses in the United States, I investigate the strategic adaptation of labour militancy and how these strikes overcome the limitations of traditional, indefinite work stoppages. I find that fixed‐duration strikes protect the economic interests of nurses and advance their role as patient care advocates, while still imposing financial and reputational costs on employers. These findings suggest that the strategic adaptation of militant tactics, such as the strike, help labour organizations achieve revitalization outcomes like contract victories and enhanced membership activism.
Resveratrol inhibits development of colorectal adenoma via suppression of LEF1; comprehensive analysis with connectivity map
Authors: Wada Hironori , Sato Yasushi , Fujimoto Shota , Okamoto Koichi , Bando Masahiro , Kawaguchi Tomoyuki , Miyamoto Hiroshi , Muguruma Naoki , Horimoto Katsuhisa , Matsuzawa Yui , Mutoh Michihiro , Takayama Tetsuji
Published: September 2022

Although many chemopreventive studies on colorectal tumors have been reported, no effective and safe preventive agent is currently available. We searched for candidate preventive compounds against colorectal tumor comprehensively from United States Food and Drug Administration (FDA)‐approved compounds by using connectivity map (CMAP) analysis coupled with in vitro screening with colorectal adenoma (CRA) patient‐derived organoids (PDOs). We generated CRA‐specific gene signatures based on the DNA microarray analysis of CRA and normal epithelial specimens, applied them to CMAP analysis with 1309 FDA‐approved compounds, and identified 121 candidate compounds that should cancel the gene signatures. We narrowed them down to 15 compounds, and evaluated their inhibitory effects on the growth of CRA‐PDOs in vitro. We finally identified resveratrol, one of the polyphenolic phytochemicals, as a compound showing the strongest inhibitory effect on the growth of CRA‐PDOs compared with normal epithelial PDOs. When resveratrol was administered to ApcMin/+ mice at 15 or 30 mg/kg, the number of polyps (adenomas) was significantly reduced in both groups compared with control mice. Similarly, the number of polyps (adenomas) was significantly reduced in azoxymethane‐injected rats treated with 10 or 100 mg/resveratrol compared with control rats. Microarray analysis of adenomas from resveratrol‐treated rats revealed the highest change (downregulation) in expression of LEF1, a key molecule in the Wnt signaling pathway. Treatment with resveratrol significantly downregulated the Wnt‐target gene (MYC) in CRA‐PDOs. Our data demonstrated that resveratrol can be the most effective compound for chemoprevention of colorectal tumors, the efficacy of which is mediated through suppression of LEF1 expression in the Wnt signaling pathway.
Impact of stress and decision fatigue on parenting practices related to food and physical activity during COVID‐19
Authors: Angoff Harrison D. , Dial Lauren A. , State Fresno , Varga Aniko V. , Kamath Sneha , Musher‐Eizenman Dara
Published: September 2022

Background

The COVID‐19 pandemic has resulted in substantial disruptions to daily functioning and lifestyle behaviours, with negative health consequences for youth. Parents play a large role in their children's health behaviour; yet changes to parenting behaviours during the pandemic related to food and physical activity remain relatively unexplored. The present study is the first to our knowledge to examine specific changes in American parents' parenting behaviours related to food and physical activity during COVID‐19, and potential correlates of such changes, including perceived stress and decision fatigue.

Methods

A total of 140 parents (88.57% female; 88.41% White; 87.59% married; with one to five children) from middle to upper income households completed an online survey assessing demographics, perceived stress (Perceived Stress Scale), decision fatigue (Decision Fatigue Scale) and food and activity parenting behaviour changes during COVID‐19.

Results

Overall, a greater proportion of parents engaged primarily in positive (57.14%) than negative (22.86%) parenting practices related to food and physical activity during the pandemic. Moderation analyses showed that the negative relation between perceived stress and positive parental behaviour changes was stronger at higher perceived increases in decision fatigue during the pandemic.

Conclusions

In the face of a major public health crisis, adaptive parental responses may emerge, but perceived stress may inhibit such behaviour change. Perceived stress and decision fatigue may represent important explanatory factors in parental health promoting behaviours during times of uncertainty and change.
The Puzzling Chasm Between Cognitive Representations and Formal Structures of Linguistic Meanings
Authors: Mondal Prakash
Published: September 2022

Natural language meaning has properties of both (embodied) cognitive representations and formal/mathematical structures. But it is not clear how they actually relate to one another. This article argues that how properties of cognitive representations and formal/mathematical structures of natural language meaning can be united remains one of the puzzles in cognitive science. That is primarily because formal/mathematical structures of natural language meaning are abstract, logical, and truth‐conditional properties, whereas cognitive/conceptual representations are embodied and grounded in sensory‐motor systems. After reviewing the current progress, this work offers, in outline, the general formulations that show how these two different kinds of representations for semantic structures can (potentially) be unified and also proposes three desiderata for testing, in brain dynamics, the mathematical equivalence between formal symbolic representations (and their transitions), and neuronal population codes (and their transitions).
Syncarcinogenesis of natural UV radiation and polycyclic aromatic hydrocarbons in the development of squamous cell carcinomas of the skin?
Authors: Weistenhöfer Wobbeke , Lutz Regina , Hiller Julia , Schmitz‐Spanke Simone , Drexler Hans
Published: September 2022

Squamous cell carcinomas (SCC) of the skin can be induced by occupational exposures to polycyclic aromatic hydrocarbons (PAHs), as in tar and soot, or to UV radiation and can be recognized and compensated as occupational diseases. A possible syncarcinogenic effect of these exposures in the development of SCC in humans is under discussion. For the scientific validation of this question, a systematic literature search was conducted using the databases PubMed, Web of Science, and Scopus. Studies on individuals with SCC of the skin and their precursors as well as occupational, non‐occupational, or therapeutic exposure to UV radiation and PAHs were selected. In addition, animal studies with exposure to UV radiation and PAHs were evaluated. After screening the abstracts of 510 identified studies, the full texts of 131 studies were reviewed. None of the epidemiological studies provided robust evidence for a syncarcinogenesis of PAHs and UV radiation in the development of SCC of the skin in humans. Nevertheless, as there are indications for a (super‐)additive effect of UV radiation and PAH exposure from animal studies and mechanistic investigations, syncarcinogenesis seems possible. However, quantitative dose‐response relationships are lacking which would allow comparison of the onset of an adverse effect between the different exposure levels.
Interventions incorporating a multi‐disciplinary team approach and a dedicated care team can help reduce preventable hospital readmissions of people with type 2 diabetes mellitus: A scoping review of current literature
Authors: Cai James , Islam Md Shahidul
Published: September 2022

Aims

This review aimed to identify interventions that hospitals can implement to reduce preventable hospital readmissions of people with type 2 diabetes mellitus (T2DM).

Methods

A scoping review framework was utilised to inform the overall process. The electronic databases Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline, the University of New England (UNE) library search engine and Google Scholar were utilised to search for relevant literature.

Results

The results from this review demonstrate that interventions started at index admission for people diagnosed with T2DM can result in reductions in hospital readmissions. Common strategies which attributed to the success of interventions in reducing hospital readmissions of people with T2DM included a multidisciplinary team approach, a dedicated care team, certified diabetes educator appointments, basic survival skills education and influencing hospital protocol development and implementation.

Conclusion

This scoping review is an attempt at exploring and synthesising current research on interventions that hospitals can implement to reduce preventable hospital readmissions of people with T2DM.
Risk of adverse events with liraglutide in heart failure with reduced ejection fraction: A post hoc analysis of the FIGHT trial
Authors: Neves João Sérgio , Vasques‐Nóvoa Francisco , Borges‐Canha Marta , Leite Ana Rita , Sharma Abhinav , Carvalho Davide , Packer Milton , Zannad Faiez , Leite‐Moreira Adelino , Ferreira João Pedro
Published: September 2022

Aim

To perform a post hoc analysis of the FIGHT trial, evaluating the effect of liraglutide (vs. placebo) on the totality of events in patients with heart failure with reduced ejection fraction (HFrEF).

Materials and Methods

FIGHT was a double‐blind randomized controlled trial (RCT) that studied liraglutide versus placebo in 300 recently hospitalized patients with HFrEF followed for 180 days. The main outcome of the present analysis was total events of hospitalizations for heart failure (HF) or all‐cause death. Secondary outcomes included total arrhythmic events and prespecified total events of interest (arrhythmias, sudden cardiac death, acute coronary syndrome, worsening HF, cerebrovascular event, venous thromboembolism, lightheadedness, presyncope/syncope or worsening renal function). Treatment effect was evaluated with negative binomial regression.

Results

Compared to placebo, there was a trend towards increased risk with liraglutide of total HF hospitalizations or all‐cause deaths (96 vs. 143 events, incidence rate ratio [IRR] 1.41, 95% confidence interval [CI] 0.98‐2.04; P = 0.064) and total arrhythmias (21 vs. 39, IRR 1.76, 95% CI 0.92‐3.37; P = 0.088). Total prespecified events of interest were increased with liraglutide compared to placebo (196 vs. 295, IRR 1.43, 95% CI 1.06‐1.92; P = 0.018). The risk of HF hospitalizations or all‐cause deaths with liraglutide was higher among patients in New York Heart Association (NYHA) Class III to IV (IRR 1.86, 95% CI 1.21‐2.85) than in those in NYHA Class I to II (IRR 0.62, 95% CI 0.31‐1.23; interaction P = 0.008), and among patients with diabetes (interaction P = 0.051). The risk of arrhythmic events was higher among those without an implanted cardiac device (interaction P = 0.047).

Conclusions

In patients with HFrEF, liraglutide might increase the risk of cardiovascular adverse effects, an effect possibly driven by excess risk of arrhythmias and worsening HF events. As this was a post hoc analysis, these results should be interpreted as exploratory and hypothesis‐generating. Further RCTs must be conducted before drawing definitive conclusions.
The role of antiplatelet therapies on incidence and mortality of hepatocellular carcinoma
Authors: Lai Quirino , De Matthaeis Nicoletta , Finotti Michele , Galati Giovanni , Marrone Giuseppe , Melandro Fabio , Morisco Filomena , Nicolini Daniele , Pravisani Riccardo , Giannini Edoardo G. ,   the Associazione Italiana per lo Studio del Fegato (AISF) HCC Special Interest Group
Published: September 2022

Aim

To evaluate the impact of antiplatelet therapy (APT)on the incidence of hepatocellular carcinoma (HCC) and mortality following its treatment.

Methods

A systematic literature search was performed using PubMed and Cochrane Central Register of Controlled Trials Databases. Two HCC clinical settings were explored: (i) incidence, and (ii) death after any HCC treatment. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the pooled data between patients who received or did not receive APT.

Results

A total of 20 studies were identified, of whom 15 focused on HCC incidence, including 2,685,009 patients, and five on post‐treatment death, including 3281 patients. APT was associated with an overall reduced risk of HCC incidence (OR: 0.63; 95%CI = 0.51–0.79; p < 0.001) as well as of post‐treatment mortality (OR: 0.54; 95%CI = 0.35–0.83; p = 0.006).

Conclusions

Current data suggest that APT correlated with higher HCC incidence and poor overall survival following tumour treatment.
Post COVID‐19 syndrome with impairment of flow‐mediated epicardial vasodilation and flow reserve
Authors: Verma Amanda , Ramayya Tarun , Upadhyaya Anand , Valenta Ines , Lyons Maureen , Marschall Jonas , Dehdashti Farrokh , Gropler Robert J. , Woodard Pamela K. , Schindler Thomas Hellmut
Published: September 2022

Aims

The aim of this study is to evaluate whether post‐acute sequelae of COVID‐19 cardiovascular syndrome (PASC‐CVS) is associated with alterations in coronary circulatory function.

Materials and Methods

In individuals with PASC‐CVS but without known cardiovascular risk factors (n = 23) and in healthy controls (CON, n = 23), myocardial blood flow (MBF) was assessed with 13N‐ammonia and PET/CT in mL/g/min during regadenoson‐stimulated hyperemia, at rest, and the global myocardial flow reserve (MFR) was calculated. MBF was also measured in the mid and mid‐distal myocardium of the left ventricle (LV). The Δ longitudinal MBF gradient (hyperemia minus rest) as a reflection of an impairment of flow‐mediated epicardial vasodilation, was calculated.

Results

Resting MBF was significantly higher in PASC‐CVS than in CON (1.29 ± 0.27 vs. 1.08 ± 0.20 ml/g/min, p ≤ .024), while hyperemic MBFs did not differ significantly among groups (2.46 ± 0.53 and 2.40 ± 0.34 ml/g/min, p = .621). The MFR was significantly less in PASC‐CVS than in CON (1.97 ± 0.54 vs. 2.27 ± 0.43, p ≤ .031). In addition, there was a Δ longitudinal MBF gradient in PASC‐CVS, not observed in CON (−0.17 ± 0.18 vs. 0.04 ± 0.11 ml/g/min, p < .0001).

Conclusions

Post‐acute sequelae of COVID‐19 cardiovascular syndrome may be associated with an impairment of flow‐mediated epicardial vasodilation, while reductions in coronary vasodilator capacity appear predominantly related to increases in resting flow in women deserving further investigations.
A Special Case of Brennan's Index for Tests That Aim to Select a Limited Number of Students: A Monte Carlo Simulation Study
Authors: Arikan Serkan , Aybek Eren Can
Published: September 2022

Many scholars compared various item discrimination indices in real or simulated data. Item discrimination indices, such as item‐total correlation, item‐rest correlation, and IRT item discrimination parameter, provide information about individual differences among all participants. However, there are tests that aim to select a very limited number of students, examinees, or candidates for allocated schools and job positions. Thus, there is a need to evaluate the performances of CTT and IRT item discrimination indices when the test purpose is to select a limited number of students. The purpose of the current Monte Carlo study is to evaluate item discrimination indices in the case of selecting a limited number of high‐achieving students. The results showed that a special case of Brennan's index, B10–90, provided more accurate information for this specific test purpose. Additionally, the effects of various factors, such as test length, ability distributions of examinees, and item difficulty variance on item discrimination indices were investigated. The performance of each item discrimination index is discussed in detail.
Prognostic impact of epileptic seizures in multiple sclerosis varies according to time of occurrence and etiology
Authors: Selton Marion , Mathey Guillaume , Soudant Marc , Manceau Philippe , Anxionnat René , Debouverie Marc , Jonas Jacques
Published: September 2022

Background and purpose

Epileptic seizures occur more often in patients with multiple sclerosis (MS) than in the general population. Their association with the prognosis of MS remains unclear. This study was undertaken to evaluate whether epileptic seizures may be a prognostic marker of MS disability, according to when the seizure occurs and its cause.

Methods

Data were extracted from a population‐based registry of MS in Lorraine, France. Kaplan–Meier curves and log‐rank tests were used to compare the probability of different levels of irreversible handicap during the course of MS in patients who experience epileptic seizures or do not, according to the chronology and the cause of the first epileptic seizure.

Results

Among 6238 patients, 134 had experienced at least one epileptic seizure (2.1%), and 82 (1.2%) had seizures secondary to MS. Patients with epileptic seizure as a first symptom of MS (14 patients) had the same disease progression as other relapsing–remitting MS patients. Patients who developed epileptic seizures during the course of MS (68 patients) had a higher probability of reaching Expanded Disability Status Scale = 3.0 (p = 0.006), 6.0 (p = 0.003), and 7.0 (p = 0.004) than patients without an epileptic background. Patients with a history of epileptic seizures unrelated to MS also had a worse prognosis than patients without an epileptic background.

Conclusions

Epileptic seizures might be viewed as a “classic MS relapse” in terms of prognosis if occurring early in MS, or as a marker of MS severity if developing during the disease. Epileptic diseases other than MS may worsen the course of MS.
Pathways from economic hardship to couple conflict by socioeconomic status during COVID‐19 in Korea
Authors: Lee Jaerim , Yoo Jaeeon , Chin Meejung , Son Seohee , Sung Miai , Chang Young Eun
Published: September 2022

Objective

The purpose of this study was to examine the direct and indirect relationships among economic hardship, economic strain, emotional stress, and couple conflict for married Koreans during the COVID‐19 pandemic. In particular, we investigated whether these pathways were different between lower and higher socioeconomic status (SES) groups.

Background

Due to the global economic downturn brought on by COVID‐19, many couples experienced economic hardship including increased household debt, job loss, and reduced work hours. This context provides a valuable opportunity to test the family stress model (FSM) of romantic relationships, which explains the indirect pathways from economic hardship to couple‐level outcomes.

Method

We collected the data using an online survey in May 2020, when the Seoul metropolitan area experienced the first surge of COVID‐19 cases. The sample came from 605 married Korean adults (282 women, 323 men) and was analyzed using multigroup path analysis.

Results

Among the three markers of economic hardship, increased household debt had a stronger association with couple conflict for lower SES respondents directly and indirectly through elevated economic strain and emotional distress. The total effects of job loss and reduced work hours on more frequent couple conflict were stronger for the higher SES group.

Conclusion

The process from the three markers of economic hardship to couple conflict was different depending on socioeconomic resources.

Implications

Family practitioners need to consider SES variations and to work with financial counselors to better support couples with both economic and relationship difficulties.
Cultural stressors, internalizing symptoms, and parent–child alienation among Mexican‐origin adolescents
Authors: Wen Wen , Chen Shanting , Hazen‐Swann Nancy , Lorenzo‐Blanco Elma I. , Shen Yishan , Kim Su Yeong
Published: September 2022

Objective

The current study investigated the relation of various cultural stressors, parent–child alienation, and Mexican‐origin adolescents' internalizing symptoms at both between‐ and within‐person levels across the course of adolescence.

Background

Positive parent–child relationships can be a critical buffer against cultural stressors for Mexican‐origin adolescents. However, it is unclear whether low levels of parent–child alienation (a) buffer the negative effects of different types of cultural stressors on internalizing symptoms and (b) function at the individual level more generally or during specific periods when adolescents experience high cultural stressors.

Method

The current study used a three‐wave longitudinal dataset of 604 Mexican‐origin adolescents (Wave 1: Mage = 12.41, SD = 0.97, 54% female, 75% born in the United States) and conducted multilevel regression analysis.

Results

At the between‐person level, overall low parent–child alienation buffered the adverse effects of ethnic discrimination on anxiety and cultural misfit on depressive symptoms. There were no significant within‐person‐level interactions of parent–child alienation and cultural stressors on adolescent internalizing symptoms.

Implication

The findings suggest that interventions should aim to reduce parent–child alienation throughout the course of adolescence to alleviate the impact of cultural stressors on internalizing symptoms among Mexican‐origin adolescents.
ADMET study, spectroscopic characterization and effect of synthetic nitro chalcone in combination with norfloxacin, ciprofloxacin, and ethidium bromide against Staphylococcus aureus efflux pumps
Authors: Rocha Janaína E. , de Freitas Thiago S. , Xavier Jayze C. , Pereira Raimundo L. S. , Pereira Junior Francisco N. , Nogueira Carlos E. S. , Marinho Márcia M. , Bandeira Paulo N. , Rodrigues Leilane G. , Marinho Emmanuel S. , de Lacerda Bruna C. G. V. , de Andrade Edlane Martins , Teixeira Alexandre M. R. , dos Santos Hélcio S. , Coutinho Henrique D. M.
Published: September 2022

Chalcones are present in a wide variety of plants, having in their structure two aromatic rings that are linked together by a chain composed of three carbon atoms with α, β‐unsaturated to carbonyl system. Bacteria have several drug resistance mechanisms, among them the efflux pump; this mechanism, when active, is able to expel different compounds from inside bacterial cells. Several efflux pumps have already been identified for Staphylococcus aureus bacteria, including MepA and NorA. Many chalcones have been isolated and identified with various activities, such as antimicrobial. In view of this, this article aimed to evaluate the antibiotic modifying effect of chalcone (E)‐1‐(2‐hydroxyphenyl)‐3‐(3‐nitrophenyl)prop‐2‐en‐1‐one against S. aureus carrier of NorA and MepA efflux pump. Regarding the antibiotic, there was a synergism when associated with ciprofloxacin in SA‐K2068 strain, showing this chalcone as an alternative to reverse the resistance to this medicine. The physicochemical properties calculated were fundamental in the description of the predicted pharmacokinetic properties. Despite the mutagenic risk caused by the metabolic activation of nitrochalcone, it is possible to notice a pharmacological principle in a longer half‐life for the performance of biological activities. The compound has a good bioavailability, as it is highly absorbed in the intestine and easily transported by plasma proteins, in addition to not presenting neurotoxic, hepatotoxic, and cardiotoxic damage.
Only one carbon difference determines the pro‐apoptotic activity of α‐tocopheryl esters
Authors: Ray Manobendro Nath , Ozono Mizune , Nakao Michiyasu , Sano Shigeki , Kogure Kentaro
Published: September 2022

α‐Tocopheryl succinate (TS), a redox‐silent succinyl ester of natural α‐Tocopherol, has emerged as a novel anti‐cancer agent. However, the underlying mechanism is unclear. We found that the terminal dicarboxylic moiety of tocopheryl esters contributes to apoptosis induction and thus cytotoxicity. To further examine this relationship, we compared the pro‐apoptotic activity of TS, which has four carbon atoms in the terminal dicarboxylic moiety, to that of a newly synthesized, tocopheryl glutarate (Tglu), which has five. Cytotoxicity assays in vitro confirmed that TS stimulated apoptosis, while Tglu was non‐cytotoxic. In investigating biological mechanisms leading to these opposing effects, we found that TS caused an elevation of intracellular superoxide, but Tglu did not. TS increased intracellular Ca2+ in cultured cells, suggesting induction of endoplasmic reticulum (ER) stress; however, Tglu did not affect Ca2+ homeostasis. 1,4,5‐trisphosphate (IP3) receptor antagonist 2‐Aminoethyl diphenylborinate (2‐APB) decreased TS‐induced intracellular Ca2+, restored mitochondrial activity and cell viability in TS‐treated cells, establishing the ER‐mitochondria relationship in apoptosis induction. Moreover, real‐time PCR, immunostaining and Western blotting assays revealed that TS downregulated glucose‐regulated protein 78 (GRP78), which maintains ER homeostasis and promotes cell survival. Conversely, Tglu upregulates GRP78. Taken together, our results suggest a model in which TS‐mediated superoxide production and GRP78 inhibition induce ER stress, which elevates intracellular Ca2+ and depolarizes mitochondria, leading to apoptosis. Because Tglu does not affect superoxide generation and increases GRP78 expression, it inhibits ER stress and is thereby non‐cytotoxic. Our research provides insight into the structure–activity relationship of tocopheryl esters regarding the induction of apoptosis.
Reciprocal abrogation of PKM isoforms: contradictory outcomes and differing impact of splicing signal on CRISPR/Cas9 mediates gene editing in keratinocytes
Authors: Nold Simon P. , Sych Khrystyna , Imre Gergely , Fuhrmann Dominik C. , Pfeilschifter Josef , Vutukuri Rajkumar , Schnutgen Frank , Wittig Ilka , Meisterknecht Jana , Frank Stefan , Goren Itamar
Published: September 2022

The healing of wounded skin is a highly organized process involving a massive cell in‐ and outflux, proliferation and tissue remodelling. It is well accepted that metabolic constraints such as diabetes mellitus, overweight or anorexia impairs wound healing. Indeed, wound inflammation involves a boost of overall metabolic changes. As wound healing converges inflammatory processes that are also common to transformation, we investigate the functional role of the pro‐neoplastic factor pyruvate kinase (PK) M2 and its metabolic active splice variant PKM1 in keratinocytes. Particularly, we challenge the impact of reciprocal ablation of PKM1 or two expression. Here, CRISPR/Cas9 genome editing of the PKM gene in HaCaT reveals an unexpected mutational bias at the 3'SS of exon 9, whereas no preference for any particular kind of mutation at exon 10 3' splice, despite the close vicinity (400 nucleotides apart) and sequence similarity between the two sites. Furthermore, as opposed to transient silencing of PKM2, exclusion splicing of PKM2 via genome editing mutually increases PKM1 mRNA and protein expression and compensates for the absence of PKM2, whereas the reciprocal elimination of PKM1 splicing reduces PKM2 expression and impedes cell proliferation, thus unveiling an essential role for PKM1 in growth and metabolic balance of HaCaT keratinocytes.
Increased risk of dialysis circuit clotting in hemodialysis patients with COVID‐19 is associated with elevated FVIII, fibrinogen and D‐dimers
Authors: Sudusinghe Dinesha , Riddell Anne , Gandhi Tejas , Chowdary Pratima , Davenport Andrew
Published: September 2022

Introduction

Severe COVID‐19 infections increase the risk of thrombotic events and Intensive Care Units reported increased extracorporeal circuit clotting (ECC) in COVID‐19 patients with acute kidney injury. We wished to determine whether hemodialysis (HD) patients with COVID‐19 also have increased risk of circuit clotting.

Methods

We reviewed coagulation studies and HD records, 4 weeks before and after COVID‐19 polymerase chain reaction detection in HD patients between April 2020 and June 2021.

Findings

Sixty‐eight (33.5%) of 203 HD patients with COVID‐19, 65% male, mean age 64.9 ± 15.3 years, experienced some circuit clotting, and no clotting recorded prior to positive test results. In those who experienced ECC, prothrombin, activated partial thromboplastin or thrombin times were not different, whereas median factor VIII (273 [168–419] vs. 166 [139–225] IU/dl, p < 0.001), D‐dimers (2654 [1381–6019] vs. 1351 [786–2334] ng/ml, p < 0.05), and fibrinogen (5.6 ± 1.4 vs. 4.9 ± 1.4 g/L, p < 0.05) were greater. Antithrombin (94 [83–112] vs. 89 [84–103] IU/dl), protein C (102 [80–130] vs. 86 [76–106] IU/dl), protein S (65 [61–75] vs. 65 [52–79] IU/dl) and platelet counts (193 [138–243] vs. 174 [138–229] × 109/L) did not differ. On multivariable logistic analysis, circuit clotting was associated with log factor VIII (odds ratio [OR] 14.8 (95% confidence limits [95% CL] 1.12–19.6), p = 0.041), fibrinogen (OR 1.57 [95% CL 1.14–21.7], p = 0.006) and log D dimer (OR 4.8 [95% CL 1.16–12.5], p = 0.028).

Discussion

Extracorporeal circuit clotting was increased within 4 weeks of testing positive for COVID‐19. Clotting was associated with increased factor VIII, fibrinogen and D‐dimer, suggesting that the risk of circuit clotting was related to the inflammatory response to COVID‐19.
Autogenic and allogenic controls on the temporal palaeographic evolution of the Himalayan foreland basin: Insights from facies analysis of the lower Siwalik succession, Kumaun Himalaya, India
Authors: Goswami Pradeep K. , Singh Karuna
Published: September 2022

The lower Siwalik succession in the south‐central Kumaun Himalaya records Middle Miocene fluvial sedimentation in the Himalayan foreland basin, the largest foreland basin of the world. Detailed facies analysis reveals three distinct facies associations, one of which is sand dominated channel deposits, and the other two are mudstone‐sandstone, and mudstone dominated overbank deposits. The initial sedimentation in the region was in channels and frequently/extensively flooded overbank areas of a meandering/anastomosing river system. Activities along basement structures sometimes caused upheaval of the basin so that the streams got incised, and overbank areas rose up beyond the reach of flood waters. As a result, the fluvial sedimentation in these upland areas ceased, the sediments that had already deposited there were subjected to extensive pedogenesis, and occasionally reworked and redistributed by sheet flows and shallow channels. The channel pattern in the region gradually changed to braided type due to channel adjustments in response to rejuvenated tectonic activities and monsoon intensification in the hinterland. These factors caused increased influx of coarser sediments in the channels, which led to gradual steepening of the channel, and once the steepening crossed the threshold, the channel changed from meandering to braided type. Interpretation of our results is contrary to the general belief that Siwalik fluvial system changed from meandering streams to braided streams during the Middle Siwalik times, and the fluvial system in the studied part of the Siwalik basin underwent this change much earlier, during the sedimentation of Lower Siwalik.
Dimmed gene knockout shortens larval growth and reduces silk yield in the silkworm, Bombyx mori
Authors: Cao Jun , Zheng Hong‐sheng , Zhang Ran , Xu Yong‐ping , Pan Huan , Li Shan , Liu Chun , Cheng Ting‐cai
Published: September 2022

The bHLH domain transcription factor, Bombyx mori‐derived dimmed (Bmdimm), is directly regulated by the JH‐BmMet/BmSRC‐BmKr‐h1 pathway and plays a key role in regulating the expression of FibH, which codes the main component of silk protein. However, the other roles of Bmdimm in silk protein synthesis remain unclear. Here, we established a Bmdimm knockout (KO) line containing a 7‐bp deletion via CRISPR/Cas9 system, which led to the absence of the bHLH domain. The expression level of silk protein genes and silk yield decreased significantly in the Bmdimm KO line. Moreover, knocking out Bmdimm led to shortened larval stages and significant weight loss in larvae and adults. Bmdimm was found to be highly expressed in the silk gland, but it was also expressed in the fat body. The expression level of Bmkr‐h1 in the fat body was significantly downregulated in the Bmdimm KO line. Exogenous JHA treatment upregulated Bmkr‐h1 and rescued the phenotype of larval growth in the Bmdimm KO line. In conclusion, knocking out Bmdimm led to a shortened larval stage via the inhibition of Bmkr‐h1 expression, then reduced silk yield. These findings help to elucidate the regulatory mechanism of fibroin synthesis and larval development in silkworms.
A novel fabrication strategy for alloyed Cd–Zn–S quantum dots–embedded glass with efficient red emission
Authors: Wang Jiancheng , Zhou Beiying , Zhao Yuye , Ma Jiaxin , Hu Xiaobo , Wang Lianjun , Jiang Wan
Published: September 2022

Quantum dots–embedded glasses (QDEGs) can combine the unique optical properties of QDs with high physicochemical stability and good mechanical properties of glasses, which have been widely investigated and applied in lighting and display. However, precise controlling the concentration and size distribution of QDs, and precipitating QDs with desired compositions or multicomponents in glass are still challenges for the traditional melt‐quenching method. Herein, a series of alloyed Cd–Zn–S QDEGs from green to red emission is successfully prepared via a novel fabrication strategy for the first time. Specifically, the solid‐solution precursors crack during the sintering process to form the well‐dispersed QDs with a narrow distribution, attributing to the gradient sulfur composition and the shearing force induced by the thermal migration of sulfur vacancies. Significantly, the quantum yield of Cd0.5Zn0.5S QDEG could reach 30%, among the top results of efficient red‐emissive QDEG materials. Finally, using QDEGs as light converters, a UV‐pumped warm white light–emitting diode with a correlated color temperature of 4238 K was achieved, which demonstrate the potential applications of the alloyed Cd–Zn–S QDEGs. These results will inspire more explorations on this fabrication strategy to develop novel QDEGs with a high optical performance for practical applications.
Patterns of variation in canal and root number in human post‐canine teeth
Authors: Gellis Jason J. , Foley Robert A.
Published: September 2022

Descriptive morphology of tooth roots traditionally focuses on number of canals and roots. However, how or if canal and root number are related is poorly understood. While it is often assumed that canal number is concomitant with root number and morphology, in practice canal number and morphology do not always covary with external root features. To investigate the relationship between canal and root number, fully developed, adult post‐canine teeth were examined and quantified from computerized tomography scans from a global sample of 945 modern humans. We tested the hypotheses that root and canal number do not follow a 1:1 ratio, that canal to root ratios differ between teeth, and that canal to root ratios differ across major human geographical groups. Results indicate that not only is root number dependent on canal number, but that this relationship becomes more variable as canal number increases, varies between individual teeth and by major geographical group, and changes as these groups increase in geographical distance from Sub‐Saharan Africa. These results show that the ratio of canal number to root number is an important indicator of variation in dental phenotypes.
Altered dynamic brain activity and its association with memory decline after night shift‐related sleep deprivation in nurses
Authors: Yan Fei‐Xin , Lin Jian‐Ling , Lin Jia‐Hui , Chen Hua‐Jun , Lin Yan‐Juan
Published: September 2022

Aims and objectives

To investigate, for the first time, aberrant time‐varying local brain activity in nurses following night shift–related sleep deprivation (SD) and its association with memory decline.

Background

Prior studies have elucidated alterations in static local brain activity resulting from SD in the occupations outside medical profession.

Design

A longitudinal study followed the STROBE recommendations.

Methods

Twenty female nurses underwent resting‐state functional magnetic resonance imaging and memory function assessment (by Complex Figure Test (CFT) and the California Verbal Learning Test, Second Edition (CVLT‐II)) twice, once in a rested wakefulness (RW) state and another after SD. By combining the sliding‐window approach and amplitude of low‐frequency fluctuation (ALFF) analysis, the dynamic ALFF (dALFF) variability was calculated to reflect the characteristics of dynamic local brain activity.

Results

Poor performance on the CFT and CVLT‐II was observed in nurses with night shift–related SD. Reduced dALFF variability was found in a set of cognition‐related brain regions (including the medial/middle/superior frontal gyrus, anterior/posterior cingulate gyrus, precuneus, angular gyrus, orbitofrontal and subgenual areas, and posterior cerebellum lobe), while increased dALFF variability was observed in the somatosensory‐related, visual and auditory regions. SD‐related dALFF variability alterations correlated with changes in subjects' performance on the CFT and CVLT‐II.

Conclusions

Night shift–related SD disturbed dynamic brain activity in high cognitive regions and induced compensatory reactions in primary perceptual cortex. Identifying dALFF variability abnormalities may broaden our understanding of neural substrates underlying SD‐related cognitive alterations, especially memory dysfunction.

Relevance to clinical practice

Night shift–related SD is as an important occupational hazard affecting brain function in nurses. The effective countermeasure addressing the adverse outcomes of SD should be advocated for nurses.

Patient or public contribution

Patients or public were not involved in the design and implementation of the study or the analysis and interpretation of the data.
Outcomes of farm compared to nonfarm pediatric injuries: A propensity‐matched analysis
Authors: Larkins Michael C. , Khanchandani Ashish , Tumin Dmitry , Greene Erika , Ledoux Matthew , Longshore Shannon
Published: September 2022

Objectives

Pediatric farm‐related injuries are rare but tend to be severe relative to other types of pediatric injury and may result in worse clinical outcomes. However, the comparison of farm and nonfarm injuries is confounded by different injury mechanisms, patient characteristics, and treating facilities. Therefore, we used propensity score matching to compare outcomes of pediatric farm and nonfarm injuries in the United States.

Methods

Data were obtained from the 2017‐2019 Trauma Quality Program database. Farm as compared to nonfarm injury was defined as the location of an injury and served as the independent variable analyzed in this study. The outcome variables analyzed were in‐hospital mortality, hospital length of stay (LOS), and admission to the intensive care unit (ICU).

Results

We identified 2,040 farm injuries and 201,865 nonfarm injuries meeting inclusion criteria. In this cohort, the mortality rate was 1%, median LOS was 2 days, and 14% of patients were admitted to the ICU. In the propensity‐matched analysis (including 2,039 farm cases matched to 2,039 nonfarm controls), farm as compared to nonfarm injuries were associated with 5% longer LOS (95% CI: 1%, 8%; P = .01), but not mortality or ICU admission.

Conclusions

In a propensity‐matched analysis, pediatric farm injuries resulted in prolonged hospital stay compared to nonfarm injuries. Identifying patient‐ and health care system‐level factors contributing to prolonged LOS may help optimize the care of children injured on farms.
MELD score < 18 rule out 28‐day ACLF development among inpatients with hepatitis B‐related previous compensated liver disease
Authors: Qi Tingting , Zhu Congyan , Wang Jiapeng , Li Beiling , Huang Zuxiong , Zhu Zhibin , Tu Minghan , Deng Guohong , Zheng Xin , Huang Yan , Meng Zhongji , Wang Xianbo , Qian Zhiping , Li Hai , Gao Yanhang , Liu Feng , Shang Jia , Shi Yu , Lu Xiaobo , Wang Shaoyang , Li Hai , Chen Jinjun
Published: September 2022

The acute‐on‐chronic liver failure (ACLF) development is highly dynamic. Currently, no satisfactory algorithm identifies patients with HBV at risk of this complication. The aim of the study was to characterize ACLF development in hospitalized HBV‐related patients without previous decompensation and to test the performance of traditional prognostic models in ruling out ACLF development within 28 days on admission we conducted a cohort study. Two multi‐center cohorts with hospitalized HBV‐related previous compensated patients were analyzed. Performances of MELD, MELD‐Na, CLIF‐C AD, and CLIF‐C ACLF‐D in ruling out ACLF development within 28 days were compared and further validated by ROC analyses. In the derivation cohort (n = 892), there were 102 patients developed ACLF within 28 days, with profound systemic inflammatory levels and higher 28‐day mortality rate (31.4% vs. 1.0%) than those without ACLF development. The MELD score (cut‐off = 18) achieved acceptable missing rate (missed/total ACLF development) at 2.9%. In the validation cohort (n = 1656), the MELD score (<18) was able to rule out ACLF development within 28 days with missing rate at 3.0%. ACLF development within 28 days were both lower than 1% (0.6%, derivation cohort; 0.5%, validation cohort) in patients with MELD < 18. While in patients with MELD ≥ 18, 26.6% (99/372, derivation cohort) and 17.8% (130/732, validation cohort) developed into ACLF within 28 days, respectively. While MELD‐Na score cut‐off at 20 and CLIF‐AD score cut‐off at 42 did not have consistent performance in our two cohorts. MELD < 18 was able to safely rule out patients with ACLF development within 28 days in HBV‐related patients without previous decompensation, which had a high 28‐day mortality.
Police redistricting reforms and urban governance
Authors: Gordon Daanika , Davis‐Pait Anthony
Published: September 2022

Police redistricting reforms are surprisingly understudied. While many understand redistricting in other realms as a mechanism of social inclusion and exclusion, police redistricting is often overlooked as merely technocratic. We argue that, in fact, police redistricting reforms are substantively and theoretically important because they articulate urban policy amid the pressures of neoliberal governance. Redistricting defines the functions and activities of the police, responds to political and economic pressures, and redistributes resources across racial spaces. To illustrate, we analyze publicly available materials describing 43 police redistricting reforms in 35 major cities in the United States. We find in these reforms an enduring emphasis on the role of the police as emergency service providers. Urban austerity and growth politics inflect redistricting and impact the distribution of police service across the city. While redistricting can theoretically result in more equitable policing, it can also amplify racial inequities by triaging resources toward downtowns and predominantly white neighborhoods, at the expense of police response in communities of color. We call for more attention to police redistricting as an arena of urban governance.