bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicted heart mass based on ideal body weight for donor‐to‐recipient size matching
Authors: Ahmad Danial , Brodie Andrew , Pritting Christopher , Rajapreyar Indranee , Rame J. Eduardo , Rajagopal Keshava , Entwistle John W. , Massey Howard , Tchantchaleishvili Vakhtang
Published: November 2023

Background

Predicted heart mass (PHM) is a commonly used tool for donor‐to‐recipient size matching. However, incorporating body weight as part of PHM can be considered problematic given its high variability, and low metabolic nature of fat. We sought to assess whether substituting the actual donor and recipient weight with the ideal body weight (IBW) would affect the association of donor‐to‐recipient PHM ratio with 1‐year and overall survival after heart transplantation.

Methods

The United Network for Organ Sharing (UNOS) database was queried for adult patients who received a primary heart transplant between January 2000 and September 2021.

Results

Both PHM and ideal PHM (IPHM) ratios were associated with one‐year (PHM: p = .003; IPHM: p = .0007) and overall (PHM: p = .02; IPHM: p = .02) survival. In the continuous analysis with restricted cubic splines, both PHM (p = .0003) and IPHM (p = .00001) were associated with relative hazards of death.

Conclusion

IPHM is significantly associated with post‐transplant survival and may be a useful compliment to PHM.
Understanding habitat selection of range‐expanding populations of large carnivores: 20 years of grey wolves (Canis lupus) recolonizing Germany
Authors: Planillo Aimara , Wenzler‐Meya Moritz , Reinhardt Ilka , Kluth Gesa , Michler Frank‐Uwe , Stier Norman , Louvrier Julie , Steyer Katharina , Gillich Benjamin , Rieger Siegfried , Knauer Felix , Kuemmerle Tobias , Kramer‐Schadt Stephanie
Published: November 2023

Aim

The non‐stationarity in habitat selection of expanding populations poses a significant challenge for spatial forecasting. Focusing on the grey wolf (Canis lupus) natural recolonization of Germany, we compared the performance of different distribution modelling approaches for predicting habitat suitability in unoccupied areas. Furthermore, we analysed whether grey wolf showed non‐stationarity in habitat selection in newly colonized areas, which will impact the predictions for potential habitat.

Location

Germany.

Methods

Using telemetry data as presence points, we compared the predictive performance of five modelling approaches based on combinations of distribution modelling algorithms—GLMM, MaxEnt and ensemble modelling—and two background point selection strategies. We used a homogeneous Poisson point process to draw background points from either the minimum convex polygons derived from telemetry or the whole area known to be occupied by wolves. Models were fit to the data of the first years and validated against independent data representing the expansion of the species. The best‐performing approach was then used to further investigate non‐stationarity in the species' response in spatiotemporal restricted datasets that represented different colonization steps.

Results

While all approaches performed similarly when evaluated against a subset of the data used to fit the models, the ensemble model based on integrated data performed best when predicting range expansion. Models for subsequent colonization steps differed substantially from the global model, highlighting the non‐stationarity of wolf habitat selection towards human disturbance during the colonization process.

Main Conclusions

While telemetry‐only data overfitted the models, using all available datasets increased the reliability of the range expansion forecasts. The non‐stationarity in habitat selection pointed to wolves settling in the best areas first, and filling in nearby lower‐quality habitat as the population increases. Our results caution against spatial extrapolation and space‐for‐time substitutions in habitat models, at least with expanding species.
Effects of land use and soil properties on taxon richness and abundance of soil assemblages
Authors: Burton Victoria J. , Baselga Andrés , De Palma Adriana , Phillips Helen R. P. , Mulder Christian , Eggleton Paul , Purvis Andy
Published: November 2023

Land‐use change and habitat degradation are among the biggest drivers of aboveground biodiversity worldwide but their effects on soil biodiversity are less well known, despite the importance of soil organisms in developing soil structure, nutrient cycling and water drainage. Combining a global compilation of biodiversity data from soil assemblages collated as part of the PREDICTS project with global data on soil characteristics, we modelled how taxon richness and total abundance of soil organisms have responded to land use. We also estimated the global Biodiversity Intactness Index (BII)—the average abundance and compositional similarity of taxa that remain in an area, compared to a minimally impacted baseline, for soil biodiversity. This is the first time the BII has been calculated for soil biodiversity. Relative to undisturbed vegetation, soil organism total abundance and taxon richness were reduced in all land uses except pasture. Soil properties mediated the response of soil biota, but not in a consistent way across land uses. The global soil BII in cropland is, on average, a third of that originally present. However, in grazed sites the decline is less severe. The BII of secondary vegetation depends on age, with sites with younger growth showing a lower BII than mature vegetation. We conclude that land‐use change has reduced local soil biodiversity worldwide, and this further supports the proposition that soil biota should be considered explicitly when using global models to estimate the state of biodiversity.
Further studies on histamine catabolism in vivo
Authors: REILLY MARGARET A. , SCHAYER R. W.
Published: November 2023

Histamine catabolism in vivo was studied in mice and rats; tissues from animals killed 2·5 min after intravenous injection of 14C‐histamine were assayed for 14C‐histamine and total 14C. Aminoguanidine, a diamine oxidase inhibitor, and methylhistamine, an inhibitor of the histamine methylating enzyme, were used to evaluate the roles of these enzymes in individual tissues.

Mouse liver and lung appeared to catabolize exogenous histamine rapidly and completely by methylation. In vivo histamine methylating activity was also found in mouse muscle, heart, kidney and lymph node, but not in stomach or intestine.

In rats 14C‐histamine was inactivated more slowly than in mice. Catabolism was most rapid in intestine where both diamine oxidase and methylating activities were found. Liver had only diamine oxidase activity. Heart showed no catabolism but had extraordinary ability to extract 14C‐histamine from blood.

The in vivo evaluation of histamine methylation by individual mouse and rat tissues agrees closely with in vitro findings by another laboratory.

Aminoguanidine reduced uptake of blood 14C‐histamine by some tissues presumably by occupying sites where histamine is normally bound.

The marked differences between tissues of mice and rats in destroying 14C‐histamine support earlier evidence that there is no apparent relationship between histamine catabolism and function.

Urine from mice with both major catabolic pathways blocked showed evidence of an abnormal excretory product of 14C‐histamine. Paper chromatograms of urine of male and female mice showed no evidence of a sex difference in catabolism of injected 14C‐histamine.

A procedure which may permit evaluating contributions of individual tissues to histamine formation in vivo is presented.

Pretreatment of mice with antihistamines, or with a histamine analogue, betahistine, did not significantly affect the rate of in vivo 14C‐histamine inactivation.
Resistance to β‐adrenoceptor stimulants (a possible explanation for the rise in asthma deaths)
Authors: CONOLLY M. E. , DAVIES D. S. , DOLLERY C. T. , GEORGE C. F.
Published: November 2023

Resistance to isoprenaline has been produced in man and dog by prolonged exposure to the same, or the pharmacologically similar compounds, terbutaline and isoetharine.

In guinea‐pigs, pretreatment with these agents increases asthma mortality provoked by histamine which suggests that this resistance may reduce the effectiveness of endogenous sympathetic drive to the bronchi.

Possible mechanisms by which the asthma death rate could be increased are discussed.

It is suggested that a drug‐induced cross resistance to endogenous sympathetic stimulation could have led to a deterioration of the asthmatic state in patients using the pressurized aerosols of sympathomimetic bronchodilators and that this might account for the rise in asthma death rate.
Cross-modal Semantically Augmented Network for Image-text Matching
Authors: Yao Tao , Li Yiru , Li Ying , Zhu Yingying , Wang Gang , Yue Jun
Published: November 2023

Image-text matching plays an important role in solving the problem of cross-modal information processing. Since there are nonnegligible semantic differences between heterogenous pairwise data, a crucial challenge is how to learn a unified representation. Existing methods mainly rely on the alignment between regional image features and corresponding entity words. However, the regional features in the image are often more concerned with the foreground entity information, and the attribute information of the entities and the relational information are ignored. How to effectively integrate entity-attribute alignment and relationship alignment has not been fully studied. Therefore, we propose a Cross-Modal Semantically Augmented Network for Image-Text Matching (CMSAN), which combines the relationships between entities in the image with the semantics of relational words in the text. CMSAN (1) proposes an adaptive word-type prediction model that classifies the words into four types, i.e., entity word, attribute word, relation word, and unnecessary word. It can align different image features at multiple levels. CMSAN (2) designs a sophisticated relationship alignment module and an entity-attribute alignment module that maximizes the exploitation of the semantic information, which enables the model to have more discriminative power and further improves the matching accuracy.
Can Biologics Be Discontinued in Patients with Psoriatic Arthritis in Stable Remission? A Prospective Single‐CenterClinical and Ultrasound Study
Authors: Graceffa Dario , Sperati Francesca , Bonifati Claudio , Spoletini Gabriele , Elia Fulvia , Caterino Mauro , Cristaudo Antonio , Morrone Aldo
Published: November 2023

Biologic disease‐modifying antirheumatic drugs (bDMARDs) and particularly tumor necrosis factor inhibitors (TNFi) have dramatically changed the natural history of psoriatic arthritis (PsA), making complete clinical remission possible in most patients. However, TNFi drugs are not without potential adverse effects such as increased infectious risk. In addition, their extensive use is associated with a significant economic burden. This prospective longitudinal cohort study involving 45 PsA patients treated with TNFi in stable remission aimed to evaluate by both clinical examination and ultrasound timing and predictive factors of disease relapse after discontinuation of TNFi treatment. Thirty‐nine (86.6%) of 45 enrolled patients experienced disease relapse during the follow‐up period, while six patients (13.4%) maintained remission beyond the scheduled 104 weeks. The median survival time of drug‐free remission after TNFi discontinuation was 24 weeks (95% confidence interval (CI): 22.6–25.4). Disease relapse was characterized by marked clinical and ultrasound worsening of dermatologic and rheumatologic conditions. However, resuming previously discontinued treatment allowed all patients to quickly regain clinical remission. Interestingly, axial involvement was a key feature of the symptomatological pattern of disease relapse, being the main reason for treatment restart in 26% of our cohort. Based on a multivariate Cox model, three variables (VAS pain, tender joint count, and swollen joint count) of the clinical assessment performed at the time point of TNFi treatment onset negatively influenced the time to disease relapse. In conclusion, temporary discontinuation of TNFi drugs is feasible and relatively safe. However, as few predictors of the risk and timing of disease relapse have been identified, patients should be closely monitored when therapy is discontinued.
Effect of Local Ketamine Subcutaneous Injection at the Incision Site in Reducing the Postoperative Pain Score after Transabdominal Hysterectomy
Authors: Eftekhar Negar , Eslami Babak , Orandi Amir Hossein , Chabouk Leila , Ghotbizadeh Vahdani Fahimeh , Mohammad khani Hoda , Amoozadeh Laya
Published: November 2023

Background. Pain control after operations is essential in decreasing the patient recovery period and potential morbidity. Prescribing opiates is very effective, but significant side effects accompany them. This study aims to examine the effect of local ketamine infiltration in decreasing pain intensity in patients undergoing transabdominal hysterectomy. Methods. In this double-blind, randomized, controlled clinical trial, a total of 92 patients undergoing transabdominal hysterectomy aged 30–60 years were selected and divided into two intervention and control groups randomly. For the intervention group, ketamine was injected subcutaneously into the incision site at a dose of 0.5 mg/kg after the operation. In the control group, 5 mg normal saline was used in the same method. Postoperative pain intensity was measured using the visual analog scale (VAS: 0–10). The pain score and dose of administered opioids were documented at 1, 2, 4, 6, 12, and 24 hours and compared between the two groups. Results. Postoperative pain intensity was significantly lower in the intervention group than in the control group, except for hour 24. The mean amounts of administered opioids were significantly lower in the intervention group at hours 6 and 12, as well as the total amount of used opioids, and no significant side effects were documented. Conclusion. Local ketamine subcutaneous injection in the incisional site is effective and is a safe procedure for reducing pain scores in patients who underwent a transabdominal hysterectomy.
A dual-loop feedback trajectory tracking control for rock drilling hydraulically driven manipulator
Authors: Chen Zixuan , Wu Jinglai , Liao Jinjun , Wang Yongsheng , Zhang Yunqing
Published: November 2023

This paper is devoted to proposing a feedback trajectory tracking control method for hydraulically driven rock drilling robotic manipulators. The rock drilling robot has a large-scale long boom and multiple joints (6R-2P), so the deformation of the arm may not be neglected. A kinematic model with the flexible deformation of the boom is developed by adding a modified coordinate transformation matrix to the general model. Each joint motion is determined by solving the inverse kinematic model in an optimization algorithm, which aims at minimizing the positional error and smoothing the motion. A dual-loop feedback controller is proposed to track the end-effector’s position and orientation. Based on the model predictive control (MPC) method, the inner-loop controller controls the cylinder motion by controlling the cylinder motion. The outer-loop controller uses the fuzzy-PID control to correct the position error which is caused by the inner-loop controller. Several reference trajectories are designed to validate the effectiveness of the proposed dual-loop control strategy, which demonstrates it has higher accuracy and lower control fluctuation than single-loop and other dual-loop controllers.
Safety of inter-facility transport strategies for patients referred for severe acute respiratory distress syndrome
Authors: Haoutar Malik , Pinero David , Yonis Hodane , Cesareo Eric , Mezidi Mehdi , Peguet Olivier , Tazarourte Karim , Pozzi Matteo , Dubien Pierre-Yves , Richard Jean-Christophe , Bitker Laurent
Published: November 2023

Background

Inter-facility transport of patients with acute respiratory distress syndrome (ARDS) in the prone position (PP) is a high-risk situation, compared to other strategies. We aimed to quantify the prevalence of complications during transport in PP, compared to transports with veno-venous extracorporeal membrane oxygenation (VV-ECMO) or in the supine position (SP).

Methods

We performed a retrospective, single center cohort study in Lyon university hospital, France. We included patients ≥ 16 years with ARDS (Berlin definition) transported to an ARDS referral center between 01/12/2016 and 31/12/2021. We compared patients transported in PP, to those transported in SP without VV-ECMO, and those transported with VV-ECMO (in SP), by a multidisciplinary and specialized medical transport team, including an emergency physician and an intensivist. The primary outcome was the rate of transport-related complications (hypoxemia, hypotension, cardiac arrest, cannula or tube dislodgement) in each study groups, compared using a Fisher test.

Results

One hundred thirty-four patients were enrolled (median PaO2/FiO2 70 [58–82] mmHg), of which 11 (8%) were transported in PP, 44 (33%) with VV-ECMO, and 79 (59%) in SP. The most frequent risk factor for ARDS in the PP group was bacterial pneumonitis, and viral pneumonitis in the other 2 groups. Transport-related complications occurred in 36% (n = 4) of transports in PP, compared to 39% (n = 30) in SP and 14% (n = 6) with VV-ECMO, respectively (p = 0.33). VV-ECMO implantation after transport was not different between SP and PP patients (n = 7, 64% vs. n = 31, 39%, p = 0.19).

Conclusions

In the context of a specialized multi-disciplinary ARDS transport team, transport-related complication rates were similar between patients transported in PP and SP, while there was a trend of lower rates in patients transported with VV-ECMO.
Prediction of incidence of neurological disorders in HIV-infected persons in Taiwan: a nested case–control study
Authors: Weng Ya-Wei , Lee Susan Shin-Jung , Tsai Hung-Chin , Hsu Chih-Hui , Lin Sheng-Hsiang
Published: November 2023

Background

Neurological disorders are still prevalent in HIV-infected people. We aimed to determine the prevalence of neurological disorders and identify their risk factors in HIV-infected persons in Taiwan.

Methods

We identified 30,101 HIV-infected people between 2002 and 2016 from the National Health Insurance Research Database in Taiwan, and analyzed the incidence of neurological disorders. We applied a retrospective, nested case–control study design. The individuals with (case group) and without (control group) a neurological disorder were then matched by age, sex and time. Factors associated with neurological disorders were analyzed using a conditional logistic regression model, and a nomogram was generated to estimate the risk of developing a neurological disorder.

Results

The incidence of neurological disorders was 13.67 per 1000 person-years. The incidence remained stable during the observation period despite the use of early treatment and more tolerable modern anti-retroviral therapy. The conditional logistic regression model identified nine clinical factors and comorbidities that were associated with neurological disorders, namely age, substance use, traumatic brain injury, psychiatric illness, HIV-associated opportunistic infections, frequency of emergency department visits, cART adherence, urbanization, and monthly income. These factors were used to establish the nomogram.

Conclusion

Neurological disorders are still prevalent in HIV-infected people in Taiwan. To efficiently identify those at risk, we established a nomogram with nine risk factors. This nomogram could prompt clinicians to initiate further evaluations and management of neurological disorders in this population.
Challenges in diagnosis and health care in polycystic ovary syndrome in Canada: a patient view to improve health care
Authors: Sydora Beate C. , Wilke Michaelann S. , McPherson Maggie , Chambers Sarah , Ghosh Mahua , Vine Donna F.
Published: November 2023

Background

Polycystic Ovary Syndrome (PCOS) is the most common endocrine-metabolic disorder affecting health and quality of life of those affected across the lifespan. We currently have limited evidence-based data on the experience of those living with PCOS in the health care system including diagnosis, health concerns and disease management. The aim of this study was to assess the perceptions of health status, health care experience and disease management support in those affected by PCOS in Alberta, Canada.

Methods

An online questionnaire was completed via REDCap by individuals self-reporting a diagnosis of PCOS. Question categories included demographics, symptoms of PCOS and time to confirm a diagnosis, follow-up care, health concerns, and information resources. Descriptive statistics were used and thematic analyses was applied to open-response questions.

Results

Responses from 194 participants living in Canada (93% in Alberta) were included. The average age was 34 ± 8 years and BMI was 35 ± 9. Menstrual irregularity was identified in 84% of respondents as the first symptom noticed and the primary reason for seeking a medical consultation. A PCOS diagnosis occurred on average 4.3 years following awareness of first symptoms and required consultation with more than one primary care provider for 57% of respondents. Half (53%) of respondents reported not receiving a referral to specialists for follow-up care and 70% were not informed about long-term health morbidity such as diabetes or cardiovascular disease. Most respondents (82%) did their own research about PCOS using on-line sources, academic literature and advice from peer support. The participant themes from open questions for improving health care included more resources and support, increased and reliable information, better education and training for clinicians, timely diagnosis, prompt referrals to specialists, and generally more compassion and empathy to the challenges faced by those managing their disease.

Conclusion

Our findings highlight the health concerns and challenges in health care for those with PCOS. In Alberta, Canada we have identified major gaps in health care including a timely diagnosis, follow up care and supports, and multidisciplinary care. This evidence-based data can be used to inform development of pathways to improve the health care experience in those affected by PCOS.
Circulating tumor DNA landscape and prognostic impact of acquired resistance to targeted therapies in cancer patients: a national center for precision medicine (PRISM) study
Authors: Bayle Arnaud , Belcaid Laila , Palmieri Lola-Jade , Teysonneau Diego , Cousin Sophie , Spalato-Ceruso Mariella , Aldea Mihaela , Vasseur Damien , Alame Melissa , Blouin Laura , Soubeyran Isabelle , Nicotra Claudio , Ngocamus Maud , Hollebecque Antoine , Loriot Yohann , Besse Benjamin , Lacroix Ludovic , Rouleau Etienne , Barlesi Fabrice , Andre Fabrice , Italiano Antoine
Published: November 2023

Background

Despite the effectiveness of the various targeted therapies currently approved for solid tumors, acquired resistance remains a persistent problem that limits the ultimate effectiveness of these treatments. Polyclonal resistance to targeted therapy has been described in multiple solid tumors through high-throughput analysis of multiple tumor tissue samples from a single patient. However, biopsies at the time of acquired resistance to targeted agents may not always be feasible and may not capture the genetic heterogeneity that could exist within a patient.

Methods

We analyzed circulating tumor DNA (ctDNA) with a large next-generation sequencing panel to characterize the landscape of secondary resistance mechanisms in two independent prospective cohorts of patients (STING: n = 626; BIP: n = 437) with solid tumors who were treated with various types of targeted therapies: tyrosine kinase inhibitors, monoclonal antibodies and hormonal therapies.

Results

Emerging alterations involved in secondary resistance were observed in the plasma of up 34% of patients regardless of the type of targeted therapy. Alterations were polyclonal in up to 14% of patients. Emerging ctDNA alterations were associated with significantly shorter overall survival for patients with some tumor types.

Conclusion

This comprehensive landscape of genomic aberrations indicates that genetic alterations involved in secondary resistance to targeted therapy occur frequently and suggests that the detection of such alterations before disease progression may guide personalized treatment and improve patient outcome.
Strategies to improve the care of older adults 50 years and above living with HIV in Uganda
Authors: Mbalinda Scovia Nalugo , Lusota Derrick Amooti , Muddu Martin , Musoke David , Nyashanu Mathew
Published: November 2023

Introduction

With effective antiretroviral therapy (ART), many persons living with HIV (PLHIV) live to old age. Caring for aged PLHIV necessitates the engagement of caregivers and patients to establish agreed-upon goals of treatment. However, there is limited literature on friendly and centered models of care for elderly PLHIV. We explored strategies to improve care in HIV clinics among PLHIV aged 50 years and above in Uganda.

Methods

We conducted 40 in-depth interviews in two hospitals with elderly PLHIV aged 50 years and above who had lived with HIV for more than ten years. We explored strategies for improving care of elderly PLHIV at both health facility and community levels. The in-depth interviews were audio-recorded and transcribed verbatim. The thematic approach guided data analysis.

Results

The elderly PLHIV suggested the following strategies to improve their care: creating geriatric clinics; increasing screening tests for non-communicable diseases in the ART clinics; community and home-based ART delivery; workshops at health facilities to provide health education on aging effectively; creating community support groups; financial assistance for the elderly PLHIV and advances in science.

Conclusions

There is need to improve community HIV care especially for the elderly and social and economic support in the community. Involving the elderly PLHIV in developing strategies to improve their health goes a long way to improve the patients' quality of care. There is a need to incorporate the raised strategies in HIV care or older adults.
Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study)
Authors: Corsini Iuri , Rodriguez-Fanjul Javier , Raimondi Francesco , Boni Luca , Berardi Alberto , Aldecoa-Bilbao Victoria , Alonso-Ojembarrena Almudena , Ancora Gina , Aversa Salvatore , Beghini Renzo , Meseguer Nerea Bilbao , Capasso Letizia , Chesi Francesca , Ciarcià Martina , Concheiro Ana , Corvaglia Luigi , Ficial Benjamim , Filippi Luca , Carballal Jesus Fuentes , Fusco Monica , Gatto Sara , Ginovart Gemma , Gregorio-Hernández Rebeca , Lista Gianluca , Sánchez-Luna Manuel , Martini Silvia , Massenzi Luca , Miselli Francesca , Mercadante Domenica , Mosca Fabio , Palacio Marta Teresa , Perri Alessandro , Piano Francesca , Prieto Marcelino Pumarada , Fernandez Lorena Rodeno , Risso Francesco Maria , Savoia Marilena , Staffler Alex , Vento Giovanni , Dani Carlo
Published: November 2023

Background

The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT.

Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group.

Methods/design

In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks’ gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group.

Discussion

Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores.

Trial registration

ClinicalTrials.gov identifier NCT05198375. Registered on 20 January 2022.
Expression analysis suggests that DNMT3L is required for oocyte de novo DNA methylation only in Muridae and Cricetidae rodents
Authors: Behluli Lirik , Fontanilla Alyssa M. , Andessner-Angleitner Laura , Tolar Nikolas , Molina Julia M. , Gahurova Lenka
Published: November 2023

Background

During early mammalian development, DNA methylation undergoes two waves of reprogramming, enabling transitions between somatic cells, oocyte and embryo. The first wave of de novo DNA methylation establishment occurs in oocytes. Its molecular mechanisms have been studied in mouse, a classical mammalian model. Current model describes DNA methyltransferase 3A (DNMT3A) and its cofactor DNMT3L as two essential factors for oocyte DNA methylation—the ablation of either leads to nearly complete abrogation of DNA methylation. However, DNMT3L is not expressed in human oocytes, suggesting that the mechanism uncovered in mouse is not universal across mammals.

Results

We analysed available RNA-seq data sets from oocytes of multiple mammals, including our novel data sets of several rodent species, and revealed that Dnmt3l is expressed only in the oocytes of mouse, rat and golden hamster, and at a low level in guinea pigs. We identified a specific promoter sequence recognised by an oocyte transcription factor complex associated with strong Dnmt3l activity and demonstrated that it emerged in the rodent clade Eumuroida, comprising the families Muridae (mice, rats, gerbils) and Cricetidae (hamsters). In addition, an evolutionarily novel promoter emerged in the guinea pig, driving weak Dnmt3l expression, likely without functional relevance. Therefore, Dnmt3l is expressed and consequently plays a role in oocyte de novo DNA methylation only in a small number of rodent species, instead of being an essential pan-mammalian factor. In contrast to somatic cells, where catalytically inactive DNMT3B interacts with DNMT3A, forming a heterotetramer, we did not find evidence for the expression of such inactive Dnmt3b isoforms in the oocytes of the tested species.

Conclusions

The analysis of RNA-seq data and genomic sequences revealed that DNMT3L is likely to play a role in oocytes de novo DNA methylation only in mice, rats, gerbils and hamsters. The mechanism governing de novo DNA methylation in the oocytes of most mammalian species, including humans, occurs through a yet unknown mechanism that differs from the current model discovered in mouse.
Evaluation of surgical revascularization procedure outcomes for adult Moyamoya disease: a computed tomography perfusion-based study
Authors: Yuan Xuexia , Yu Hao , Sun Zhanguo , Wu Jiaxing , Gao Lingyun , Chong Zhen , Jin Feng , Chen Yueqin , Liu Deguo
Published: November 2023

Background

The effectiveness of surgical interventions, whether direct or indirect, for Moyamoya disease (MMD) remains controversial. This study aims to investigate CT perfusion (CTP) as an objective method to evaluate the outcomes of different surgical modalities for adult MMD.

Methods

The clinical and imaging data of 41 patients who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass and 43 who received encephaloduroarteriosynangiosis (EDAS) were retrospectively analyzed. Intra- and intergroup differences in the Modified Rankin Scale (mRS) score, the change in clinical symptoms, collateral grade, and CTP parameters pre- and postoperatively were compared.

Results

The overall level of the change in clinical symptoms in the STA-MCA group was higher than in the EDAS group (p < 0.05). In the operative area, the relative cerebral blood flow (rCBF) was significantly higher whereas the relative time to peak (rTTP) and the relative mean transit time (rMTT) were significantly lower in the STA-MCA and EDAS groups postoperatively than preoperatively (all p < 0.05). In the ipsilateral frontal lobe and basal ganglia, the postoperative rCBF was significantly higher, and the rTTP was significantly lower than the preoperative in the STA-MCA group (all p < 0.05). The postoperative rCBF improvement was higher in each brain area for STA-MCA than in the EDAS group (all p < 0.05).

Conclusion

Highlighting the utility of CTP, this study demonstrates its effectiveness in assessing postoperative cerebral hemodynamic changes in adult MMD patients. STA-MCA yielded a larger postoperative perfusion area and greater improvement compared to EDAS, suggesting CTP’s potential to elucidate symptom variation between two surgical revascularization procedures.

Critical relevance statement

We analyzed computed tomography perfusion parameters in pre- and postoperative adult Moyamoya disease patients undergoing superficial temporal artery-middle cerebral artery bypass and encephaloduroarteriosynangiosis. Our findings suggest computed tomography perfusion’s potential in objectively elucidating symptom variations between these surgical revascularization approaches for MMD.

Key points

• Postoperative perfusion improvement is only confined to the operative area after EDAS.

• Besides the operative area, postoperative perfusion in the ipsilateral frontal lobe and basal ganglia was also improved after STA-MCA.

• The degree of perfusion improvement in each brain area in the STA-MCA group was generally greater than that in the EDAS group.

Graphical Abstract
Improving speech recognition systems for the morphologically complex Malayalam language using subword tokens for language modeling
Authors: Manohar Kavya , A R Jayan , Rajan Rajeev
Published: November 2023

This article presents the research work on improving speech recognition systems for the morphologically complex Malayalam language using subword tokens for language modeling. The speech recognition system is built using a deep neural network–hidden Markov model (DNN-HMM)-based automatic speech recognition (ASR). We propose a novel method, syllable-byte pair encoding (S-BPE), that combines linguistically informed syllable tokenization with the data-driven tokenization method of byte pair encoding (BPE). The proposed method ensures words are always segmented at valid pronunciation boundaries. On a text corpus that has been divided into tokens using the proposed method, we construct statistical n-gram language models and assess the modeling effectiveness in terms of both information-theoretic and corpus linguistic metrics. A comparative study of the proposed method with other data-driven (BPE, Morfessor, and Unigram), linguistic (Syllable), and baseline (Word) tokenization algorithms is also presented. Pronunciation lexicons of subword tokenized units are built with pronunciation described as graphemes. We develop ASR systems employing the subword tokenized language models and pronunciation lexicons. The resulting ASR models are comprehensively evaluated to answer the research questions regarding the impact of subword tokenization algorithms on language modeling complexity and on ASR performance. Our study highlights the strong performance of the hybrid S-BPE tokens, achieving a notable 10.6% word error rate (WER), which represents a substantial 16.8% improvement over the baseline word-level ASR system. The ablation study has revealed that the performance of S-BPE segmentation, which initially underperformed compared to syllable tokens with lower amounts of textual data for language modeling, exhibited steady improvement with the increase in LM training data. The extensive ablation study indicates that there is a limited advantage in raising the n-gram order of the language model beyond $$n=3$$

n
=
3

. Such an increase results in considerable model size growth without significant improvements in WER. The implementation of the algorithm and all associated experiments are available under an open license, allowing for reproduction, adaptation, and reuse.
The run test for two samples in the presence of uncertainty
Authors: Aslam Muhammad
Published: November 2023

The run test, which examines whether two samples selected from the same population are random, has been employed. However, the current run test for two samples is based on the assumption of certainty, which is not always valid in practical scenarios. This paper aims to introduce a modified version of the run test for two samples that account for uncertainty. We will develop a statistical approach for the run test that considers uncertain factors such as sample size, level of significance, and observations. To evaluate the effectiveness of the proposed test, we analyze wind power and photovoltaic power data. The analysis of these variables demonstrates that they are randomly selected from the population. The results indicate that the proposed run test is well-suited for addressing uncertainty in renewable energy. By employing this modified test, we can effectively assess the randomness of samples and make reliable conclusions in uncertain conditions.
The climate variability trio: stochastic fluctuations, El Niño, and the seasonal cycle
Authors: Stuecker Malte F.
Published: November 2023

Climate variability has distinct spatial patterns with the strongest signal of sea surface temperature (SST) variance residing in the tropical Pacific. This interannual climate phenomenon, the El Niño-Southern Oscillation (ENSO), impacts weather patterns across the globe via atmospheric teleconnections. Pronounced SST variability, albeit of smaller amplitude, also exists in the other tropical basins as well as in the extratropical regions. To improve our physical understanding of internal climate variability across the global oceans, we here make the case for a conceptual model hierarchy that captures the essence of observed SST variability from subseasonal to decadal timescales. The building blocks consist of the classic stochastic climate model formulated by Klaus Hasselmann, a deterministic low-order model for ENSO variability, and the effect of the seasonal cycle on both of these models. This model hierarchy allows us to trace the impacts of seasonal processes on the statistics of observed and simulated climate variability. One of the important outcomes of ENSO’s interaction with the seasonal cycle is the generation of a frequency cascade leading to deterministic climate variability on a wide range of timescales, including the near-annual ENSO Combination Mode. Using the aforementioned building blocks, we arrive at a succinct conceptual model that delineates ENSO’s ubiquitous climate impacts and allows us to revisit ENSO’s observed statistical relationships with other coherent spatio-temporal patterns of climate variability—so called empirical modes of variability. We demonstrate the importance of correctly accounting for different seasonal phasing in the linear growth/damping rates of different climate phenomena, as well as the seasonal phasing of ENSO teleconnections and of atmospheric noise forcings. We discuss how previously some of ENSO’s relationships with other modes of variability have been misinterpreted due to non-intuitive seasonal cycle effects on both power spectra and lead/lag correlations. Furthermore, it is evident that ENSO’s impacts on climate variability outside the tropical Pacific are oftentimes larger than previously recognized and that accurately accounting for them has important implications. For instance, it has been shown that improved seasonal prediction skill can be achieved in the Indian Ocean by fully accounting for ENSO’s seasonally modulated and temporally integrated remote impacts. These results move us to refocus our attention to the tropical Pacific for understanding global patterns of climate variability and their predictability.
Exploring the multifaceted roles of mathematics learning in predicting students' computational thinking competency
Authors: Lee Silvia Wen-Yu , Tu Hsing-Ying , Chen Guang-Lin , Lin Hung-Ming
Published: November 2023

Background

There exist shared competencies between computational thinking (CT) and mathematics, and these two domains also mutually benefit from various teaching approaches. However, the linkages between mathematics and computational thinking lack robust empirical support, particularly from student-centered learning perspectives. Our study aimed to enhance our understanding of the connections between students' mathematics learning and computational thinking. To assess students' mathematics learning, we measured their beliefs about mathematics learning and their level of mathematical literacy (ML). Our hypothesis posited that students' beliefs concerning mathematics learning, encompassing their views on the nature of mathematics and their attitude towards the subject, can both directly and indirectly influence their CT, with ML serving as a mediating factor. Our data were gathered through surveys and tests administered to eighth- and ninth-grade students. Data were analyzed using partial least squares–structural equation modeling (PLS–SEM).

Results

The evaluation of the measurement model indicated strong internal consistency for each construct. Both convergent and discriminant validity were also established. Upon assessing the structural model, it was found that beliefs about the nature of mathematics positively predicted attitudes towards mathematics, and this belief also indirectly predicted ML through positive attitudes towards mathematics. In addition, ML directly and positively predicted both CT subscales. Notably, a comprehensive mediating effect of ML on beliefs about mathematics learning and CT was identified in the analysis.

Conclusions

This study advances the understanding of the relationships between mathematics learning and CT. We have further confirmed the importance of mathematical literacy in predicting CT and its mediating role between beliefs about mathematics learning and CT. It is suggested that teachers could promote students’ CT competence by enhancing their mathematical literacy or integrating mathematics and CT into the same learning activities. Finally, we propose that upcoming investigations treat CT assessments as formative constructs, diverging from their reflective counterparts.
Polymer composite microspheres loading
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Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer
Authors: Xiao Liu , Li Yuhao , Geng Ruiman , Chen Lihong , Yang Peng , Li Mingyu , Luo Xia , Yang Yuchuan , Li Lin , Cai Huawei
Published: November 2023

Background

Transarterial radioembolization (TARE) with
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Y-labeled glass and resin microspheres is one of the primary treatment strategies for advanced-stage primary and metastatic hepatocellular carcinoma (HCC). However, difficulties of real-time monitoring post administration and embolic hypoxia influence treatment prognosis. In this study, we developed a new biodegradable polymer microsphere that can simultaneously load
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Lu and MgO nanoparticle, and evaluated the TARE therapeutic efficacy and biosafety of
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Lu-PDA-CS-MgO microspheres for HCC treatment.

Methods

Chitosan microspheres were synthesized through emulsification crosslink reaction and then conducted surface modification with polydopamine (PDA). The
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Lu and nano MgO were conjugated to microspheres using active chemical groups of PDA. The characteristics of radionuclide loading efficiency, biodegradability, blood compatibility, and anti-tumor effectwere evaluated both in vitro and in vivo. SPECT/CT imaging was performed to monitor bio-distribution and bio-stability of
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Lu-PDA-CS-MgO after TARE treatment. The survival duration of each rat was monitored. HE analysis, TUNEL analysis, immunohistochemical analysis, and western blot analysis were conducted to explore the anti-tumor effect and mechanism of composited microspheres. Body weight, liver function, blood routine examination were monitored at different time points to evaluate the bio-safety of microspheres.

Results

The composite
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Lu-PDA-CS-MgO microsphere indicated satisfactory degradability, biocompatibility, radionuclide loading efficiency and radiochemical stability in vitro. Cellular evaluation showed that
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Lu-PDA-CS-MgO had significant anti-tumor effect and blocked tumor cell cycles in S phase. Surgical TARE treatment with
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Lu-PDA-CS-MgO significantly prolonged the medial survival time from 49 d to 105 d, and effectively inhibited primary tumor growth and small metastases spreading. Moreover, these microspheres indicated ideal in vivo stability and allowed real-time SPECT/CT monitoring for up to 8 weeks. Immunostaining and immunoblotting results also confirmed that
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Lu-PDA-CS-MgO had potential in suppressing tumor invasion and angiogenesis, and improved embolic hypoxia in HCC tissues. Further evaluations of body weight, blood test, and pathological analysis indicated good biosafety of
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Lu-PDA-CS-MgO microspheres in vivo.

Conclusion

Our study demonstrated that
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Lu-PDA-CS-MgO microsphere hold great potential as interventional brachytherapy candidate for HCC therapy.

Graphical Abstract

Polymer composite microspheres loading
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Lu radionuclide and MgO nanoparticles for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer.
Illicium verum anticancer activity against MDA-MB-231 cell line
Authors: Pahore Asra Khan , Khan Shagufta , Karim Nasim
Published: November 2023

Objective: To evaluate the anticancer activity of methanolic extract of Illicium verum against triple-negative breast cancer MDA-MB-231 cell line.

Methods: A cell culture experimental study was carried out at Pharmacology department of Bahria University Medical and Dental College (January to June 2021) in collaboration with Aga Khan University, Karachi, Pakistan. Cell viability and proliferation assays were used to quantify dead and alive cells by utilizing a tetrazolium assay and an enzyme immunosorbent plate reader was used to calculate their absorbance. For the apoptosis initiation assay, these cells were dyed with a fluorescent stain and observed for fluorescence and apoptosis. During cell viability testing, various I. verum methanolic extract doses (0.125, 0.25, 0.5, 1, 3, 6, 12, and 25µg/ml) were employed to treat MDA-MB-231 cells, while the IC50 dose of 2.8µg/ml was used for both the cell proliferation and apoptosis initiation assays.

Results: In the cell viability assay, all I. verum methanolic extract doses exhibited a substantial decrease in the viability of MDA-MB-231 cells (less than 0.01 p-value). In cell proliferation assay and apoptosis initiation, the IC50 dose of 2.8µg/ml of I. verum methanolic extract also exhibited a substantial decrease in cell division (less than 0.01 p-value) and the initiation of apoptosis in MDA-MB-231 cells.

Conclusion: Illicium verum methanolic extract have strong anticancer activity against triple-negative breast cancer MDA-MB-231 cell line through cytotoxicity, proliferation reduction, and apoptosis initiation mechanisms.

doi: https://doi.org/10.12669/pjms.40.1.7860

How to cite this: Pahore AK, Khan S, Karim N. Illicium verum anticancer activity against MDA-MB-231 cell line. Pak J Med Sci. 2024;40(1):---------. doi: https://doi.org/10.12669/pjms.40.1.7860

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.