bluuebunny/crossref_metadata_2025 huggingface dataset:
The importance of instrumental assessment in disorders of consciousness: a comparison between American, European, and UK International recommendations
Authors: Magnani F. G. , Barbadoro F. , Cacciatore M. , Leonardi M.
Published: August 2022

The use of instrumental tools for improving both the diagnostic accuracy and the prognostic soundness in patients with disorders of consciousness (DOC) plays an important role. However, the most recent international guidelines on DOC published by the American and the European Academies of Neurology and by the UK Royal College of Physicians contain heterogeneous recommendations on the implementation of these techniques in the clinical routine for both diagnosis and prognosis. With the present work, starting from the comparison of the DOC guidelines’ recommendations, we look for possible explanations behind such discrepancies considering the adopted methodologies and the reference health systems that could have affected the guidelines’ perspectives. We made a provocative argument about the need to find the most appropriate common methodology to retrieve and grade the evidence, increase the meta-analytic studies, and reduce the health policies that influence on the guidelines development that, in turn, should inform the health policies with the strongest scientific evidence.
Clonal evolution in primary breast cancers under sequential epirubicin and docetaxel monotherapy
Authors: Venizelos Andreas , Engebrethsen Christina , Deng Wei , Geisler Jürgen , Geisler Stephanie , Iversen Gjertrud T. , Aas Turid , Aase Hildegunn S. , Seyedzadeh Manouchehr , Steinskog Eli Sihn , Myklebost Ola , Nakken Sigve , Vodak Daniel , Hovig Eivind , Meza-Zepeda Leonardo A. , Lønning Per E. , Knappskog Stian , Eikesdal Hans P.
Published: August 2022

Background

Subclonal evolution during primary breast cancer treatment is largely unexplored. We aimed to assess the dynamic changes in subclonal composition of treatment-naïve breast cancers during neoadjuvant chemotherapy.

Methods

We performed whole exome sequencing of tumor biopsies collected before, at therapy switch, and after treatment with sequential epirubicin and docetaxel monotherapy in 51 out of 109 patients with primary breast cancer, who were included in a prospectively registered, neoadjuvant single-arm phase II trial.

Results

There was a profound and differential redistribution of subclones during epirubicin and docetaxel treatment, regardless of therapy response. While truncal mutations and main subclones persisted, smaller subclones frequently appeared or disappeared. Reassessment of raw data, beyond formal mutation calling, indicated that the majority of subclones seemingly appearing during treatment were in fact present in pretreatment breast cancers, below conventional detection limits. Likewise, subclones which seemingly disappeared were still present, below detection limits, in most cases where tumor tissue remained. Tumor mutational burden (TMB) dropped during neoadjuvant therapy, and copy number analysis demonstrated specific genomic regions to be systematically lost or gained for each of the two chemotherapeutics.

Conclusions

Sequential epirubicin and docetaxel monotherapy caused profound redistribution of smaller subclones in primary breast cancer, while early truncal mutations and major subclones generally persisted through treatment.

Trial registration

ClinicalTrials.gov, NCT00496795, registered on July 4, 2007.
Identification of influential probe types in epigenetic predictions of human traits: implications for microarray design
Authors: Hillary Robert F. , McCartney Daniel L. , McRae Allan F. , Campbell Archie , Walker Rosie M. , Hayward Caroline , Horvath Steve , Porteous David J. , Evans Kathryn L. , Marioni Riccardo E.
Published: August 2022

Background

CpG methylation levels can help to explain inter-individual differences in phenotypic traits. Few studies have explored whether identifying probe subsets based on their biological and statistical properties can maximise predictions whilst minimising array content. Variance component analyses and penalised regression (epigenetic predictors) were used to test the influence of (i) the number of probes considered, (ii) mean probe variability and (iii) methylation QTL status on the variance captured in eighteen traits by blood DNA methylation. Training and test samples comprised ≤ 4450 and ≤ 2578 unrelated individuals from Generation Scotland, respectively.

Results

As the number of probes under consideration decreased, so too did the estimates from variance components and prediction analyses. Methylation QTL status and mean probe variability did not influence variance components. However, relative effect sizes were 15% larger for epigenetic predictors based on probes with known or reported methylation QTLs compared to probes without reported methylation QTLs. Relative effect sizes were 45% larger for predictors based on probes with mean Beta-values between 10 and 90% compared to those based on hypo- or hypermethylated probes (Beta-value ≤ 10% or ≥ 90%).

Conclusions

Arrays with fewer probes could reduce costs, leading to increased sample sizes for analyses. Our results show that reducing array content can restrict prediction metrics and careful attention must be given to the biological and distribution properties of CpG probes in array content selection.
Application of Weizmannia coagulans in the medical and livestock industry
Authors: Wang Linhao , Wang Jie , Du Liyu , Fang Xiang , Liao Zhenlin
Published: August 2022

Purpose

Products enriched with probiotics have always been fashionable. Weizmannia coagulans has become a hot research topic in the academic community due to their multiple functional properties and high resistance to stress, which can retain their activity in a variety of harsh environments. This review aims to evaluate the probiotic effects of different strains of Weizmannia coagulans in animals and humans and to inspire better exploitation of the value of this strain.

Methods

This review summarizes the latest research progress of Weizmannia coagulans from two major applications in animal breeding and human health.

Results

The functional properties of Weizmannia coagulans are extensively recognized. In animals, the strain can promote nutrient absorption, reduce mortality, and enhance the slaughter rate in livestock and poultry. In humans, the strain can be used to treat gastrointestinal disorders, immunomodulation, depressive symptoms, and non-alcoholic fatty liver. Weizmannia coagulans is projected as an ideal substitute for antibiotics and other chemical drugs.

Conclusion

Despite the outstanding functional properties of Weizmannia coagulans, there are numerous strains of Weizmannia coagulans and significant differences between strains in functional and physiological properties. Currently, there are few literature reports on the probiotic mechanism and functional gene identification of Weizmannia coagulans, which is crucial for the commercialization of Weizmannia coagulans and the benefit of human society.
Optimizing pediatric asthma education using virtual platforms during the COVID-19 pandemic
Authors: Radhakrishnan Dhenuka , Higginson Andrea , Thipse Madhura , Tessier Marc , Radhakrishnan Arun
Published: August 2022

Background

We compared patient and caregiver knowledge and confidence for managing asthma, and participant experiences when comprehensive asthma education was delivered in person versus in the virtual setting.

Methods

We performed a multi-methods study using structured surveys and qualitative interviews to solicit feedback from patients and caregivers following participation in a comprehensive asthma education session between April 2018 and October 2021. We compared participant knowledge and confidence for managing asthma as well as user experience when the education was attended in-person or virtually. Quantitative responses were summarized descriptively, and qualitative feedback was analyzed for major themes.

Results

Of 100 caregivers/patients who completed post education satisfaction surveys and interviews, 52 attended in person and 48 virtually, with the mean age of patients being 6.7 years (range: 1.2–17.0). Participant reported gains in knowledge and confidence for asthma management were not different between groups and 65.2% preferred attending virtual asthma education. The majority of participants described virtual education as a safer modality that was more convenient and accessible.

Conclusions

We demonstrated the successful implementation of a novel, virtual asthma education program for patients and caregivers of children with asthma. Both virtual and in-person delivered asthma education were equally effective for improving perceived knowledge and confidence for asthma self-management and virtual education was considered safer, more convenient and accessible. Virtual asthma education offers an attractive and effective option for improving the reach of quality asthma education programs and may allow more children/patients to benefit.
Modulation of osteogenic differentiation by Escherichia coli-derived recombinant bone morphogenetic protein-2
Authors: Kim Nam-Hyun , Jung Seon-Kyong , Lee Juno , Chang Pahn-Shick , Kang Seung-Hoon
Published: August 2022

Recombinant human bone morphogenetic protein-2 (rhBMP-2), a key regulator of osteogenesis, induces the differentiation of mesenchymal cells into cartilage or bone tissues. Early orthopedic and dental studies often used mammalian cell-derived rhBMP-2, especially Chinese hamster ovary (CHO) cells. However, CHO cell-derived rhBMP-2 (C-rhBMP-2) presents disadvantages such as high cost and low production yield. To overcome these problems,Escherichia coli-derived BMP-2 (E-rhBMP-2) was developed; however, the E-rhBMP-2-induced signaling pathways and gene expression profiles during osteogenesis remain unclear. Here, we investigated the E-rhBMP-2-induced osteogenic differentiation pattern in C2C12 cells and elucidated the difference in biological characteristics between E-rhBMP-2 and C-rhBMP-2 via surface plasmon resonance, western blotting, qRT-PCR, RNA-seq, and alkaline phosphatase assays. The binding affinities of E-rhBMP-2 and C-rhBMP-2 towards BMP receptors were similar, both being confirmed at the nanomolecular level. However, the phosphorylation of Smad1/5/9 at 3 h after treatment with E-rhBMP-2 was significantly lower than that on treatment with C-rhBMP-2. The expression profiles of osteogenic marker genes were similar in both the E-rhBMP-2 and C-rhBMP-2 groups, but the gene expression level in the E-rhBMP-2 group was lower than that in the C-rhBMP-2 group at each time point. Taken together, our results suggest that the osteogenic signaling pathways induced by E-rhBMP-2 and C-rhBMP-2 both follow the general Smad-signaling pathway, but the difference in intracellular phosphorylation intensity results in distinguishable transcription profiles on osteogenic marker genes and biological activities of each rhBMP-2. These findings provide an extensive understanding of the biological properties of E-rhBMP-2 and the signaling pathways during osteogenic differentiation.
The psychological subtype of intimate partner violence and its effect on mental health: a systematic review with meta-analyses
Authors: Dokkedahl S. B. , Kirubakaran R. , Bech-Hansen D. , Kristensen T. R. , Elklit A.
Published: August 2022

Purpose

The present study examines the association between psychological violence and posttraumatic stress disorder (PTSD), depression, and anxiety, while comparing the specific subtypes of psychological violence and simultaneously focusing on methodological shortcomings.

Method

A systematic review and random-effects meta-analyses were applied on the three main outcomes: PTSD, depression, and anxiety. Four electronic databases were searched (PsycINFO, PubMed, EMBASE, and Web of Science), and a total of 194 studies were included (k = 149 for meta-analyses). GRADEpro was used to evaluate the certainty of the evidence from the meta-analyses.

Results

Psychological violence had strong associations with the three main outcomes, with the strongest association for PTSD in both female and male victims. Coercive control was particularly associated with PTSD for female victims, while emotional/verbal and dominance/isolation had the strongest association with depression. Although the identified studies were characterized by gender bias, psychological violence appear to affect male mental health too.

Discussion

Findings from the meta-analyses support the notion that psychological violence is a traumatic experience, which is strongly association with PTSD and other common mental health problems linked to trauma. GRADEpro rated the certainty of evince to be low, and thus, our confidence in the estimated effect is limited. Gender bias, the applied terminology, and other methodological shortcomings are discussed. Despite the substantial amount of research on this topic, more research is needed before we can draw any final conclusions on the effect of psychological violence on mental health.
Evaluating methodological quality of prognostic prediction models on patient reported outcome measurements after total hip replacement and total knee replacement surgery: a systematic review protocol
Authors: Chang Wei-Ju , Naylor Justine , Natarajan Pragadesh , Liu Victor , Adie Sam
Published: August 2022

Background

Prediction models for poor patient-reported surgical outcomes after total hip replacement (THR) and total knee replacement (TKR) may provide a method for improving appropriate surgical care for hip and knee osteoarthritis. There are concerns about methodological issues and the risk of bias of studies producing prediction models. A critical evaluation of the methodological quality of prediction modelling studies in THR and TKR is needed to ensure their clinical usefulness. This systematic review aims to (1) evaluate and report the quality of risk stratification and prediction modelling studies that predict patient-reported outcomes after THR and TKR; (2) identify areas of methodological deficit and provide recommendations for future research; and (3) synthesise the evidence on prediction models associated with post-operative patient-reported outcomes after THR and TKR surgeries.

Methods

MEDLINE, EMBASE, and CINAHL electronic databases will be searched to identify relevant studies. Title and abstract and full-text screening will be performed by two independent reviewers. We will include (1) prediction model development studies without external validation; (2) prediction model development studies with external validation of independent data; (3) external model validation studies; and (4) studies updating a previously developed prediction model. Data extraction spreadsheets will be developed based on the CHARMS checklist and TRIPOD statement and piloted on two relevant studies. Study quality and risk of bias will be assessed using the PROBAST tool. Prediction models will be summarised qualitatively. Meta-analyses on the predictive performance of included models will be conducted if appropriate. A narrative review will be used to synthesis the evidence if there are insufficient data to perform meta-analyses.

Discussion

This systematic review will evaluate the methodological quality and usefulness of prediction models for poor outcomes after THR or TKR. This information is essential to provide evidence-based healthcare for end-stage hip and knee osteoarthritis. Findings of this review will contribute to the identification of key areas for improvement in conducting prognostic research in this field and facilitate the progress in evidence-based tailored treatments for hip and knee osteoarthritis.

Systematic review registration

PROSPERO registration number CRD42021271828.
Spatial patterns, causes and characteristics of the cultural landscape of the Road of Tang Poetry based on text mining: take the Road of Tang Poetry in Eastern Zhejiang as an example
Authors: Xi Xuesong , An Xingrun , Zhang Guangming , Liang Shifan
Published: August 2022

The Road of Tang Poetry in Eastern Zhejiang is a poetic cultural route linked by Tang poetry which is the pinnacle of ancient Chinese poetry history, and is a cluster of cultural landscapes where nature and humanity blend together under the narrative of Tang poetry. The research has mined and collated the text information of poems, such as trails, persons, places and landscapes, in 1593 poems written by 451 poets of the Tang Dynasty in Eastern Zhejiang, and discerned the overall route of the Road of Tang Poetry in Eastern Zhejiang based on the spatial location of all the text information in GIS. The spatial distribution pattern of the cultural landscape of the Road of Tang Poetry is analyzed and summarized from four levels: natural landscape, Buddhist and Taoist cultural landscape, celebrity cultural landscape and folk cultural landscape. The complex social network relationship between “poet-person” and “poet-landscape” is shown through the Gephi tools. The four causes and two characteristics of the Road of Tang poetry in Eastern Zhejiang are explained from the perspective of the logic of mathematical statistics.
Morphofunctional changes following adenotonsillectomy of obstructive sleep apnea children: a case series analysis
Authors: Tinano Mariana M. , Becker Helena M. G. , Franco Letícia P. , dos Anjos Claudia P. G. , Ramos Vinícius M. , Nader Carolina M. F. F. , Godinho Joana , de Párcia Gontijo Henrique , Souki Bernardo Q.
Published: August 2022

Objective

To perform a case series analysis of the changes in the pulmonary artery systolic pressure (PASP), nasal inspiratory flow (NIF), upper airway volume, obstructive apnea/hypopnea index (OAHI), and the maxillomandibular three-dimensional (3D) morphology after adenotonsillectomy (T&A) of obstructive sleep apnea children (OSA).

Materials and methods

Retrospective assessment of files from 1002 children screened between 2012 and 2020 in a hospital-based mouth-breather referral center. From this universe, 15 obstructive sleep apnea children (7 females; 8 males), ages 4.1 to 8.9 years old (mean age of 5.4 years ± 1.3), who presented indications of tonsillectomy and/or adenoidectomy were selected. The complete baseline examination (T0) was carried out before T&A and a second complete examination (T1) was made 18.7-month follow-up after T&A (ranging from 12 to 30 months). Eleven patients were submitted to T&A, and four patients had indications but did not receive authorization for surgery from the public health system. According to the protocol of the outpatient clinic for OSA patients, Doppler echocardiography, polysomnography, rhinomanometry, and computed tomography imaging was performed at (T0) and (T1).

Results

PASP decreased 16.6% after T&A. NIF increased more in T&A children (40.3%) than in non-T&A children (16.8%). The upper airway volume increased in T&A and non-T&A children, but greater volumetric gain (45.6%) was found in the nasopharynx of T&A patients. OAHI did not change in six T&A children (55%) and three non-T&A children (75%). The maxilla displaced downward and backward relative to the cranial base in six T&A children (55%) and two untreated children (50%). Nine of the T&A children (85%) and three untreated children (75%) presented extensive condylar growth and increased mandibular length. The qualitative 3D assessment showed similar morphological 3D changes in T&A and non-T&A patients.

Conclusion

Pulmonary artery systolic pressure decreased, nasal inspiratory flow increased, and nasopharynx volume increased following adenotonsillectomy, but obstructive apnea/hypopnea index and maxillomandibular morphology were similar in surgical and non-surgical patients.
Succinate: A Serum Biomarker of SDHB-Mutated Paragangliomas and Pheochromocytomas
Authors: Lamy Constance , Tissot Hubert , Faron Matthieu , Baudin Eric , Lamartina Livia , Pradon Caroline , Al Ghuzlan Abir , Leboulleux Sophie , Perfettini Jean-Luc , Paci Angelo , Hadoux Julien , Broutin Sophie
Published: August 2022

Context

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors that are frequently associated with succinate dehydrogenase (SDH) germline mutations. When mutated, SDH losses its function, thus leading to succinate accumulation.

Objective

In this study, we evaluated serum succinate levels as a new metabolic biomarker in SDHx-related carriers.

Methods

Retrospective monocentric study of 88 PPGL patients (43 sporadic, 35 SDHB, 10 SDHA/C/D), 17 tumor-free familial asymptomatic carriers (13 SDHB, 4 SDHC/D), and 60 healthy controls. Clinical, biological, and imaging data were reviewed. Serum succinate levels (n = 280) were quantified by an ultra-performance liquid chromatography coupled to a tandem mass spectrometry method and correlated to SDHx mutational status, disease extension, and other biological biomarkers.

Results

Serum succinate levels > 7 μM allowed identification of tumor-free asymptomatic SDHB-mutated cases compared to a healthy control group (100% specificity; 85% sensitivity). At PPGL diagnosis, SDHB-mutated patients had a significantly increased median succinate level (14 μM) compared to sporadic patients (8 μM) (P < 0.01). Metastatic disease extension was correlated to serum succinate levels (r = 0.81). In the SDHB group, patients displaying highest tumor burdens showed significant increased succinate levels compared to the sporadic group (P < 0.0001).

Conclusions

In this pilot study, we showed that serum succinate level is an oncometabolic biomarker that should be useful to identify SDHB-related carriers. Succinate levels are also a marker of metabolic tumor burden in patients with a metastatic PPGL and a potential marker of treatment response and follow-up.
Collagen VI deficiency causes behavioral abnormalities and cortical dopaminergic dysfunction
Authors: Gregorio Ilaria , Mereu Maddalena , Contarini Gabriella , Bello Luca , Semplicini Claudio , Burgio Francesca , Russo Loris , Sut Stefania , Dall'Acqua Stefano , Braghetta Paola , Semenza Carlo , Pegoraro Elena , Papaleo Francesco , Bonaldo Paolo , Cescon Matilde
Published: August 2022

Mutations of genes coding for collagen VI (COL6) cause muscle diseases, including Ullrich congenital muscular dystrophy and Bethlem myopathy. Although COL6 genetic variants were recently linked to brain pathologies, the impact of COL6 deficiency in brain function is still largely unknown. Here, a thorough behavioral characterization of COL6-null (Col6a1–/–) mice unexpectedly revealed that COL6 deficiency leads to a significant impairment in sensorimotor gating and memory/attention functions. In keeping with these behavioral abnormalities, Col6a1–/– mice displayed alterations in dopaminergic signaling, primarily in the prefrontal cortex. In vitro co-culture of SH-SY5Y neural cells with primary meningeal fibroblasts from wild-type and Col6a1–/– mice confirmed a direct link between COL6 ablation and defective dopaminergic activity, through a mechanism involving the inability of meningeal cells to sustain dopaminergic differentiation. Finally, patients affected by COL6-related myopathies were evaluated with an ad hoc neuropsychological protocol, revealing distinctive defects in attentional control abilities. Altogether, these findings point towards a previously undescribed role for COL6 in the proper maintenance of dopamine circuitry function and its related neurobehavioral features in both mice and humans.

This article has an associated First Person interview with the first author of the paper.
Consensus guidelines on the construct validity of rodent models of restless legs syndrome
Authors: Salminen Aaro V. , Clemens Stefan , García-Borreguero Diego , Ghorayeb Imad , Li Yuqing , Manconi Mauro , Ondo William , Rye David , Siegel Jerome M. , Silvani Alessandro , Winkelman John W. , Allen Richard P. , Ferré Sergi ,   the International Restless Legs Syndrome Study Group (IRLSSG)
Published: August 2022

Our understanding of the causes and natural course of restless legs syndrome (RLS) is incomplete. The lack of objective diagnostic biomarkers remains a challenge for clinical research and for the development of valid animal models. As a task force of preclinical and clinical scientists, we have previously defined face validity parameters for rodent models of RLS. In this article, we establish new guidelines for the construct validity of RLS rodent models. To do so, we first determined and agreed on the risk, and triggering factors and pathophysiological mechanisms that influence RLS expressivity. We then selected 20 items considered to have sufficient support in the literature, which we grouped by sex and genetic factors, iron-related mechanisms, electrophysiological mechanisms, dopaminergic mechanisms, exposure to medications active in the central nervous system, and others. These factors and biological mechanisms were then translated into rodent bioequivalents deemed to be most appropriate for a rodent model of RLS. We also identified parameters by which to assess and quantify these bioequivalents. Investigating these factors, both individually and in combination, will help to identify their specific roles in the expression of rodent RLS-like phenotypes, which should provide significant translational implications for the diagnosis and treatment of RLS.
PDGFR dimer-specific activation, trafficking and downstream signaling dynamics
Authors: Rogers Madison A. , Campaña Maria B. , Long Robert , Fantauzzo Katherine A.
Published: August 2022

Signaling through the platelet-derived growth factor receptors (PDGFRs) plays a critical role in multiple cellular processes during development. The two PDGFRs, PDGFRα and PDGFRβ, dimerize to form homodimers and/or heterodimers. Here, we overcome previous limitations in studying PDGFR dimer-specific dynamics by generating cell lines stably expressing C-terminal fusions of each PDGFR with bimolecular fluorescence complementation (BiFC) fragments corresponding to the N-terminal or C-terminal regions of the Venus fluorescent protein. We find that PDGFRβ receptors homodimerize more quickly than PDGFRα receptors in response to PDGF ligand, with increased levels of autophosphorylation. Furthermore, we demonstrate that PDGFRα homodimers are trafficked and degraded more quickly, whereas PDGFRβ homodimers are more likely to be recycled back to the cell membrane. We show that PDGFRβ homodimer activation results in a greater amplitude of phospho-ERK1/2 and phospho-AKT signaling, as well as increased proliferation and migration. Finally, we demonstrate that inhibition of clathrin-mediated endocytosis leads to changes in cellular trafficking and downstream signaling, particularly for PDGFRα homodimers. Collectively, our findings provide significant insight into how biological specificity is introduced to generate unique responses downstream of PDGFR engagement.

This article has an associated First Person interview with the first author of the paper.
Intraspecific investigation of dehydration-enhanced innate immune performance and endocrine stress response to sublethal dehydration in a semi-aquatic species of pit viper
Authors: Sandfoss Mark R. , Brischoux François , Lillywhite Harvey B.
Published: August 2022

Sublethal dehydration can cause negative physiological effects, but recent studies investigating the sub-lethal effects of dehydration on innate immune performance in reptiles have found a positive correlation between innate immune response and plasma osmolality. To investigate whether this is an adaptive trait that evolved in response to dehydration in populations inhabiting water-scarce environments, we sampled free-ranging cottonmouth snakes (n=26 adult cottonmouths) from two populations inhabiting contrasting environments in terms of water availability: Snake Key (n=12), an island with no permanent sources of fresh water, and Paynes Prairie (n=14), a flooded freshwater prairie. In addition to field surveys, we manipulated the hydration state of 17 cottonmouths (Paynes Prairie n=9, Snake Key n=8) in a laboratory setting and measured the response of corticosterone and innate immune performance to dehydration with the aim of identifying any correlation or trade-offs between them. We measured corticosterone of cottonmouths at a baseline level and then again following a 60 min stress test when at three hydration states: hydrated, dehydrated and rehydrated. We found that innate immune performance improved with dehydration and then returned to baseline levels within 48 h of rehydration, which agrees with previous research in reptiles. Despite the frequent exposure of cottonmouths on Snake Key to dehydrating conditions, we did not find cottonmouths inhabiting the island to show a greater magnitude or more prolonged immune response compared with cottonmouths from Paynes Prairie. We also found a positive association between dehydration and corticosterone values.
Electric catfish hearts are not intrinsically immune to electric shocks
Authors: Welzel Georg , Schuster Stefan
Published: August 2022

High voltage electric shocks cause life threatening cardiac injuries such as sudden cardiac standstill or severe myocardial injury. Here, we analysed the physiology of the heart of the strongly electric catfish (Malapterurus beninensis) that stuns prey with high-voltage shocks but is immune to its own, as well as external, high-voltage shocks. Neither a detailed analysis of the electrocardiogram nor the structure of the heart indicated a specialized cardiac conduction system. Using a suitable perfusion system, we discovered that, despite its immunity in vivo, the explanted heart of electric catfish can readily be activated by external electrical currents and is equally sensitive to electric shock-induced arrhythmias as similar-sized goldfish hearts. The surprise thus is that the electric catfish has a vulnerable heart that requires to be protected by highly efficient but presently unknown means.
Naked-Eye-Detectable Supramolecular Sensing System for Glutaric Acid and Isophthalic Acid
Authors: Muranaka Atsuya , Ban Hayato , Naito Masaya , Miyagawa Shinobu , Ueda Masahiro , Yamamoto Shin , Harada Mei , Takaya Hikaru , Kimura Masaki , Kobayashi Nagao , Uchiyama Masanobu , Tokunaga Yuji
Published: August 2022

We report a molecular sensor, comprising a porphyrin core and four 2-aminoquinolyl groups at meso positions, for the naked-eye detection of glutaric acid and isophthalic acid, both featuring a C3 spacer between two CO2H groups. In the presence of the C3 dicarboxylic acids, solutions of the porphyrin sensor underwent significant changes in color and absorption spectra. NMR spectroscopy and X-ray crystallography revealed that the porphyrin derivative bound to two molecules of the C3 dicarboxylic acids selectively to form 1:2 complexes, which dimerized through strong π-stacking interactions. Magnetic circular dichroism (MCD) spectroscopy and density functional theory (DFT) calculations suggested that the red-shifting of the Q-bands in the absorption spectra of the porphyrin derivative arose from tilted quinolyl rings in the dimeric complexes. In addition, we found that a test strip containing the porphyrin sensor could also be used to efficiently detect glutaric acid and isophthalic acid.
Aerobic or Muscle-Strengthening Physical Activity: Which Is Better for Health?
Authors: Brellenthin Angelique G. , Bennie Jason A. , Lee Duck-chul
Published: August 2022

The Physical Activity Guidelines recommend performing 150 min of moderate- to vigorous-intensity aerobic physical activity (MVPA) per week. These guidelines also recommend muscle-strengthening physical activity (MSPA) on ≥2 d·wk−1 for additional benefits including muscular fitness and bone health. The majority of the scientific evidence supporting the PA recommendations for health comes from studies of MVPA while the possible contributions of MSPA in these findings have been overlooked historically. Emerging evidence suggests that MSPA can independently protect against major cardiometabolic risk factors, chronic diseases, and mortality. Additional data from clinical trials indicate that many of the well-known health benefits of exercise, like improvements in cardiovascular disease risk factors, are more robust with combined MVPA and MSPA. This review will clarify the relative benefits of MSPA versus MVPA on health-related outcomes to determine the best type of PA for health.
Association of mortality and endothelial dysfunction with serum ADMA level in COVID-19 patients
Authors: Karacaer Cengiz , Yaylacı Selcuk , Demirci Taner , Cekic Deniz , Suner Kezban Ozmen , Cokluk Erdem , Varım Ceyhun
Published: August 2022

Objectives: To investigate the role of asymmetric dimethylarginine (ADMA) level in predicting intensive care and mortality in patients affected with coronavirus disease 2019 (COVID-19).

Methods: This retrospective, cross-sectional study was conducted at Sakarya University Training and Research Hospital (Sakarya, Turkey) between April and August of 2020. We enrolled patients who were diagnosed with COVID-19 via real-time reverse-transcription polymerase chain reaction and admitted to the intensive care (Severe COVID-19; S-COVID) or non intensive care (Moderate COVID-19; M-COVID). We then analyzed the relationship of the ADMA level with various parameters between S-COVID and M-COVID groups.

Results: This study included 87 patients, comprising 43 females and 44 males, with a mean age of 61 and 71.50 years, respectively. The male/female distribution was 22/25 (46.8%/53.2%) in the M-COVID group and 22/18 (55%/45%) in the S-COVID group. The hospitalization time, white blood cell count, neutrophil count, lymphocyte-to-albumin ratio, international normalization ratio, D-dimer, troponin, ferritin, lactate dehydrogenase, C-reactive protein, procalcitonin, erythrocyte sedimentation rate, fibrinogen, lactate, ADMA, and mortality rate were significantly higher (p < 0.05). In contrast, lymphocyte, total cholesterol, high-density lipoprotein, calcium, and albumin values were lower (p < 0.05) in the S-COVID group than in the M-COVID group. While the mortality rate was 55% in S-COVID patients, no mortality was detected in M-COVID patients (p < 0.05). Moreover, ADMA level was 6618 ± 3000 (6400) in S-COVID patients and 5365 ± 3571 (3130) in M-COVID patients, indicating a statistically significant difference (p = 0.012).

Conclusion: The asymmetric dimethylarginine level increases in severe outcomes; hence, it can potentially predict severity in patients with COVID-19.

doi: https://doi.org/10.12669/pjms.38.7.5327

How to cite this:Karacaer C, Yaylaci S, Demirci T, Cekic D, Suner KO, Cokluk E, et al. Association of mortality and endothelial dysfunction with serum ADMA level in COVID-19 patients. Pak J Med Sci. 2022;38(7):---------. doi: https://doi.org/10.12669/pjms.38.7.5327

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Health Related Quality of Life amongst Sewerage and Sanitary Workers of Karachi, Pakistan
Authors: Fatmi Syed Ishtiaq Ahmed , Mansoori Naveed , Mubeen Syed Muhammad
Published: August 2022

Objectives: To find out the impact of occupational and socio-demographic factors on the health related quality of life of sewerage and sanitary workers in Karachi.

Methods: A cross-sectional study was conducted during 2019. Four hundred workers were chosen from five districts of Karachi using a non-probability convenient sampling technique. An Urdu version of WHO BRIEF quality of life questionnaire was used to collect the data about workers general health status and quality of life. Descriptive analysis was done and Chi-square test was used for the association of socio-demographic factors and quality of life. Multiple regression model was used to predict QOL of all domains. P-value<0.05 was considered as statistically significant.

Results: Out of 400 sanitary workers, 228 (57.0%) were sweepers and the rest 172 (43.0) were sewerage workers. The majority of the workers 321 (80.3%) were male and 246 (61.5%) were illiterate. The vast majority of the workers 386 (96.5%) were not immunized against typhoid, / hepatitis and tetanus. Ninety-one percent (91%) were not using any kind of safety gadgets while at work. Male workers, married workers of both sexes and those with some education had a little better quality of life than their counterparts. Sanitary employees likewise had a higher quality of life score than sewage workers (P-value<0.05).

Conclusion: The majority of workers, particularly sewage workers, have a very poor quality of life. Along with very bad working circumstances, their standard of living is significantly below par. They were not given any safety equipment. They were handling untreated sewage/waste with their bare hands, and they have never received a typhoid/hepatitis /tetanus vaccine.

doi: https://doi.org/10.12669/pjms.38.7.5697

How to cite this:Fatmi SIA, Mansoori N, Mubeen SM. Health Related Quality of Life amongst Sewerage and Sanitary Workers of Karachi, Pakistan. Pak J Med Sci. 2022;38(7):---------. doi: https://doi.org/10.12669/pjms.38.7.5697

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Management of concomitant strip and apical perforation in mandibular first molar
Authors: Al Attas Mustafa Hussein , Aldhelai Thiyezen Abdullah , Javed Muhammad Qasim
Published: August 2022

Iatrogenic perforation is a complication that can occur during endodontic treatment. If left untreated, it adversely affects the prognosis of the tooth. The use of optimal magnification and appropriate repair material help in achieving favourable outcome. The current case report illustrates the management of concomitant strip and apical perforation in the mesial canals of lower first molar of 13 years old paediatric patient. The management of perforations was done with MTA under 25x magnification of a dental operating microscope. The periapical radiograph and clinical investigations revealed complete bone formation at the furcal area adjacent to the repaired strip perforation and ossification of the apical lesion indicating a favourable healing outcome at 18 months of follow up.

doi: https://doi.org/10.12669/pjms.38.7.6009

How to cite this:Al-Attas MH, Aldhelai TA, Javed MQ. Management of concomitant strip and apical perforation in mandibular first molar. Pak J Med Sci. 2022;38(7):---------. doi: https://doi.org/10.12669/pjms.38.7.6009

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
INFLUENCE OF BIOTRAN ON THE PRODUCTIVITY AND QUALITY OF SPRING WHEAT GRAIN IN THE MIDDLE VOLGA REGION
Authors: Saydyasheva Galina , Zayceva Kseniya
Published: August 2022

An experiment to study the effect of plant growth regulators Biotran and Energia M on spring wheat yield was carried out in Ulyanovsk region at the experimental site of Ulyanovsk Research Institute of Agriculture - a branch of the Samsra Scientific Center of the Russian Academy of Sciences in 2019-2021. The influence of the studied preparations on the yield data and quality indicators of spring wheat grain was studied. It was established that the use of growth regulators studied in the experiment had a positive effect on the grain yield and its quality. The effective doses of the studied preparations were determined. The following were used in the experiment: growth stimulants - Energy M (standard), Biotran and a complex mineral fertilizer (Azofoska at a dose of 15 kg AI). Spring wheat cultivar Simbirtsit was sown as the studied crop. The soil of the experimental plot is represented by leached, heavy loamy chernozem. The scheme of the experiment involved the study of the following options: mineral fertilizers (factor A) - without fertilizers (0), azophoska during sowing (N15P15K15); growth regulators for pre-sowing treatment of seeds and single treatment of vegetative plants (factor B) - without treatment (0), Energy M (standard) 4 g/t + 10.0 g/ha, Biotran 5 g/t + 5.0 g/ha ha, Biotran 5 g/t + 10.0 g/ha. Pre-sowing treatment of seeds was carried out manually by the method of semidry dressing the day before sowing, with dosages recommended by the manufacturer. Spraying was carried out manually with a knapsack sprayer during the budding phase of spring wheat. The results of the research found that the increase in spring wheat yield was the largest in the variant with the use of the Biotran growth regulator at a dosage of 5 g/t (presowing seed treatment) + 10 g/ha (spraying) in all years of the experiment. On average, for three years in this variant, the yield was 1.85 t/ha against the background without the use of fertilizers and 1.94 t/ha against the fertilized background. Under the influence of the studied growth regulators, the technological and biochemical parameters of grain improved: the protein content in the grain increased by 0.3-1.4%, gluten by 0.2-1.9%, nature by 1-12 g/l.
Poetics and Aesthetics of Ch. Baudelaire’s Work and His Communicative Dialogue Trough Ages with the XXI Century Postmodernist Writers F. Beigbeder and B. Werber
Authors: Beley M. , Fonova E.
Published: August 2022

The article deals with the main features of poetics and aesthetics of Ch. Baudelaire's work, entering into communication with modern postmodernist writers through the centuries. These principles of cultural dialogue, poetics and aesthetics include dualism, supernaturalism, the principle of playing with the reader, escapism to the imaginary country of Icaria, oneiric and thanatological motifs, the peculiar chronotope of the city. The worldview principles of the work include romantic pessimism, sleepwalking, dandyism and escapism.

Contemporary French postmodernist writers B. Werber and F. Beigbeder are followers of the poetic heritage of Charles Baudelaire. In his novels one can find quotations from Baudelaire's Flowers of Evil, the author enters into a communicative dialogue with the French poet, some fragments of them even serve as epigraphs to his works. Werber's novel "The Sixth Dream" also contains direct references to the poetry of Baudelaire.

In B. Werber's Thanatonauts presents the themes of death, sleep and escapism in the compositional form of the journeys of the Thanatonaut scientists into the "space" of death. The theory of supernaturalism is embodied in the cycles of novels "About Angels" and "About the Gods", where the man appears as a decider of the fate of planets with an alternate reality. His colourful postmodern neo-mythological novels weave together different forms of art: painting, architecture and music.

In the works of F. Beigbeder widely represented the image of modern cynical urban dandy. The protagonist of his novels "99 Francs" and "Ideal", "The Man Who Cried Laughing", "Stories on Ecstasy" is a product of a consumer society era of postmodernism. He is carefree, cruel and amoral. His craving for escapism into a dream world is expressed in his infatuation with illegal substances.

The work of Werber and Beigbeder encapsulates the dualistic principle of Baudelaire, Werber's characters strive for spiritual perfection, while Beigbeder's characters engage in carnal pleasures and self-destruction. Werber and Beigbeder are the successors and heirs of Baudelaire's poetics, expressed in sensual aestheticism, numerous allusions, eclecticism, supernaturalism, an interest in the afterlife and the poetics of sleep.
Functioning of Institutional Discourses in The Communicative Space of the Popular Science Journal “Chelovek i zakon” (“Man and Law”)
Authors: Solov'eva Yu.
Published: August 2022

Discursive attribution of texts functioning in a popular science law-related journal is analyzed. The agents and target recipients of interacting discourses and models of their interaction are characterized. Means of secondary categorization and conceptualization used by the agents of the popular legal discourse to adapt legal terms for non-specialists are described. Function is determined as a classifying criterion for the different discourse and text types forming the communicative space of the journal. The author comes to the conclusion that all institutional discourses and their “hybrids” represented in a popular science law-related journal construe a certain reality where great significance is given to legal values and principles.
Design and Evaluation of Optimal Free Trials
Authors: Yoganarasimhan Hema , Barzegary Ebrahim , Pani Abhishek
Published: August 2022

Free trial promotions are a commonly used customer acquisition strategy in the Software as a Service industry. We use data from a large-scale field experiment to study the effect of trial length on customer-level outcomes. We find that, on average, shorter trial lengths (surprisingly) maximize customer acquisition, retention, and profitability. Next, we examine the mechanism through which trial length affects conversions and rule out the demand cannibalization theory, find support for the consumer learning hypothesis, and show that long stretches of inactivity at the end of the trial are associated with lower conversions. We then develop a personalized targeting policy that allocates the optimal treatment to each user based on individual-level predictions of the outcome of interest (e.g., subscriptions) using a lasso model. We evaluate this policy using the inverse propensity score reward estimator and show that it leads to 6.8% improvement in subscription compared with a uniform 30-days for-all policy. It also performs well on long-term customer retention and revenues in our setting. Further analysis of this policy suggests that skilled and experienced users are more likely to benefit from longer trials, whereas beginners are more responsive to shorter trials. Finally, we show that personalized policies do not always outperform uniform policies, and we should be careful when designing and evaluating personalized policies. In our setting, personalized policies based on other methods (e.g., causal forests, random forests) perform worse than a simple uniform policy that assigns a short trial length to all users.

This paper was accepted by Duncan Simester, marketing.

Supplemental Material: The data files and online appendices are available at https://doi.org/10.1287/mnsc.2022.4507 .
Stochastic Optimization with Decision-Dependent Distributions
Authors: Drusvyatskiy Dmitriy , Xiao Lin
Published: August 2022

Stochastic optimization problems often involve data distributions that change in reaction to the decision variables. This is the case, for example, when members of the population respond to a deployed classifier by manipulating their features so as to improve the likelihood of being positively labeled. Recent works on performative prediction identify an intriguing solution concept for such problems: find the decision that is optimal with respect to the static distribution that the decision induces. Continuing this line of work, we show that, in the strongly convex setting, typical stochastic algorithms—originally designed for static problems—can be applied directly for finding such equilibria with little loss in efficiency. The reason is simple to explain: the main consequence of the distributional shift is that it corrupts algorithms with a bias that decays linearly with the distance to the solution. Using this perspective, we obtain convergence guarantees for popular algorithms, such as stochastic gradient, clipped gradient, prox-point, and dual averaging methods, along with their accelerated and proximal variants. In realistic applications, deployment of a decision rule is often much more expensive than sampling. We show how to modify the aforementioned algorithms so as to maintain their sample efficiency when performing only logarithmically many deployments.

Funding: This work was supported by the Division of Computing and Communication Foundations [Grant 1740551] and Division of Mathematical Sciences [Grant 1651851].