bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure of artemether-lumefantrine therapy in travellers returning to Belgium with Plasmodium falciparum malaria: an observational case series with genomic analysis
Authors: Pierreux Jan , Bottieau Emmanuel , Florence Eric , Maniewski Ula , Bruggemans Anne , Malotaux Jiska , Martin Charlotte , Cox Janneke , Konopnicki Deborah , Guetens Pieter , Verschueren Jacob , Coppens Jasmine , Van Esbroeck Marjan , Mutsaers Mathijs , Rosanas-Urgell Anna
Published: December 2023

Background

Failure of artemisinin-based combination therapy is increasingly reported in patients with Plasmodium falciparum malaria in sub-Saharan Africa. We aimed to describe the clinical and genomic characteristics of recent cases of P. falciparum malaria failing artemether-lumefantrine in Belgium.

Methods

Travel-related cases of malaria confirmed at the national reference laboratory of the Institute of Tropical Medicine, Antwerp, Belgium, were reviewed. All cases for which attending clinicians reported persistence (beyond Day 3 post-treatment initiation, i.e. early failure) or recrudescence (from Day 7 to 42, i.e. late failure) of P. falciparum parasites despite adequate drug intake were analysed. Both initial and persistent/recurrent samples were submitted to next generation sequencing to investigate resistance-conferring mutations.

Results

From July 2022 to June 2023, eight P. falciparum cases of failure with artemether-lumefantrine therapy were reported (early failure = 1; late failure = 7). All travellers were returning from sub-Saharan Africa, most (6/8) after a trip to visit friends and relatives. PfKelch13 (PF3D7_1343700) mutations associated with resistance to artemisinin were found in two travellers returning from East Africa, including the validated marker R561H in the patient with early failure and the candidate marker A675V in a patient with late failure. Additional mutations were detected that could contribute to decreased susceptibility to artemisinin in another three cases, lumefantrine in six cases and proguanil in all eight participants. Various regimens were used to treat the persistent/recrudescent cases, with favourable outcome.

Conclusion

Within a 12-month period, we investigated eight travellers returning from sub-Saharan Africa with P. falciparum malaria and in whom artemether-lumefantrine failure was documented. Mutations conferring resistance to antimalarials were found in all analysed blood samples, especially against lumefantrine and proguanil, but also artemisinin. There is a pressing need for systematic genomic surveillance of resistance to antimalarials in international travellers with P. falciparum malaria, especially those experiencing treatment failure.
Silent spread of DENV-3 in Brazil: autochthonous outbreak in São Paulo after 15 years
Authors: Fujita Dennis M , Salvador Felipe S , da Silva Nali Luiz H , de Andrade Júnior Heitor F
Published: December 2023

The high incidence of dengue in Brazil and re-emergence of DENV-3 in São Paulo after a 15-year absence, coupled with the potential risk for DENV-4, may be the results from changing climate patterns favouring Aedes mosquito proliferation, allied by the resuming of domestic and international travels.
The Empire Strikes Back: A Chemical Warfare Burn 100 Years After the First World War Ending
Authors: Montanari Alvise , Costa Alfio Luca , Azzena Bruno
Published: December 2023

During the First World War, the territories that constituted the front line in North East Italy were the theaters of intense shelling. The military tactics of the time involved the use not only of conventional ammunition but also of special ammunition containing asphyxiating and blistering compounds. However, the technology of the time did not guarantee a high explosion rate, leaving a considerable quantity of unexploded material on the ground.

Although more than 100 years have passed since the end of the Great War, it is still common to find unexploded ordnance in the areas that were the site of combat. The demining campaign is still underway by the bomb squad of the Italian army with the medical support of the Military Corps of the Italian Red Cross. This case report reports the case of a young patient who came into contact with a vesicant chemical bomb along the Piave River and was subsequently admitted to the Major Burns Center of the Padua Hospital, where he was treated until full recovery. Although it is a rather rare eventuality, experiences like this provide the opportunity for the admitting surgeon to promptly and competently manage patients exposed to chemical warfare
Biomarkers of Waterpipe Tobacco Smoke Exposure: A Systematic Review and Meta-Analysis
Authors: Yan Yong Yang , Ye Fen , Ho Mu-Hsing , Yeung Karly Cheuk Yin , Lee Jung Jae
Published: December 2023

Introduction

The prevalence of waterpipe tobacco smoking is increasing globally. Biomarkers of waterpipe tobacco smoke (WTS) exposure are less studied.

Aims and Methods

To identify the types of biomarkers of WTS exposure and estimate changes in biomarker concentrations pre- to post-WTS exposure. PubMed, Embase, Web of Science, CINAHL Plus, PsycINFO, and Cochrane Library were searched for studies up to April 24, 2023. The types of biomarkers were identified. Random-effects models were used to estimate changes in biomarker concentrations pre- to post-WTS exposure.

Results

Seventy-three studies involving 3755 participants exposed to WTS (49% male, mean age: 24.8 years) and 11 types of biomarkers of WTS exposure were identified. The biomarkers included tobacco alkaloids, expired carbon monoxide (eCO), carboxyhemoglobin (COHb), tobacco-specific nitrosamines, volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), heavy metals, unmetabolized VOCs, unmetabolized PAHs, furan metabolites, and heterocyclic aromatic amines. Compared with pre-WTS exposure, eCO (breath; mean difference [MD] 27.00 ppm; 95% confidence interval [CI]: 20.91 to 33.08), COHb (blood; MD 4.30%; 95%CI: 2.57 to 6.03), COHb (breath; MD 7.14%; 95%CI: 4.96 to 9.31), nicotine (blood; MD 8.23 ng/mL; 95%CI: 6.27 to 10.19), and cotinine (urine; MD 110.40 ng/mL; 95%CI: 46.26 to 174.54) significantly increased post-WTS exposure.

Conclusions

Biomarkers of WTS exposure were systematically identified. The similarity between the biomarkers of WTS exposure and those of cigarette smoke and higher concentrations of some biomarkers post-WTS exposure underscore the need for further research on applying biomarkers in surveillance, interventions, and regulations to mitigate the harms of waterpipe tobacco smoking.

Implications

This study provides the first comprehensive overview of biomarkers investigated and available for assessing WTS exposure and their concentration changes in the human body. Researchers can use biomarkers such as eCO, COHb, nicotine, and cotinine to measure the health risks associated with WTS exposure and objectively evaluate the effectiveness of public health interventions aimed at reducing waterpipe tobacco smoking. Public health policymaking can also be informed through increased biomarker concentrations following WTS exposure, to implement regulations and public health education campaigns on limiting or preventing waterpipe tobacco smoking.
Protein sequence design on given backbones with deep learning
Authors: Liu Yufeng , Liu Haiyan
Published: December 2023

Deep learning methods for protein sequence design focus on modeling and sampling the many- dimensional distribution of amino acid sequences conditioned on the backbone structure. To produce physically foldable sequences, inter-residue couplings need to be considered properly. These couplings are treated explicitly in iterative methods or autoregressive methods. Non-autoregressive models treating these couplings implicitly are computationally more efficient, but still await tests by wet experiment. Currently, sequence design methods are evaluated mainly using native sequence recovery rate and native sequence perplexity. These metrics can be complemented by sequence-structure compatibility metrics obtained from energy calculation or structure prediction. However, existing computational metrics have important limitations that may render the generalization of computational test results to performance in real applications unwarranted. Validation of design methods by wet experiments should be encouraged.
Examining the Relationship Between Individual Patient Factors and Substantial Clinical Benefit From Telerehabilitation Among Patients With Chronic Low Back Pain
Authors: McLaughlin Kevin H , Fritz Julie M , Minick Kate I , Brennan Gerard P , McGee Terrence , Lane Elizabeth , Thackeray Anne , Bardsley Tyler , Wegener Stephen T , Hunter Stephen J , Skolasky Richard L
Published: December 2023

Objective

The coronavirus disease-2019 pandemic has facilitated the emergence of telerehabilitation, but it is unclear which patients are most likely to respond to physical therapy provided this way. The purpose of this study was to examine the relationship between individual patient factors and substantial clinical benefit from telerehabilitation among a cohort of patients with chronic low back pain (LBP).

Methods

This is a secondary analysis of data collected during a prospective longitudinal cohort study. Patients with chronic LBP (N = 98) were provided with a standardized physical therapy protocol adapted for telerehabilitation. We examined the relationship between patient factors and substantial clinical benefit with telerehabilitation, defined as a ≥50% improvement in disability at 10 weeks, measured using the Oswestry Disability Index.

Results

Sixteen (16.3%) patients reported a substantial clinical benefit from telerehabilitation. Patients reporting substantial clinical benefit from telerehabilitation had lower initial pain intensity, lower psychosocial risk per the STarT Back Screening Tool, higher levels of pain self-efficacy, and reported higher therapeutic alliance with their physical therapist compared to other patients.

Conclusion

Patients with lower psychosocial risk and higher pain-self efficacy experienced substantial clinical benefit from telerehabilitation for chronic LBP more often than other patients in our cohort. Therapeutic alliance was higher among patients who experienced a substantial clinical benefit compared to those who did not.

Impact

This study indicates that psychosocial factors play an important role in the outcomes of patients receiving telerehabilitation for chronic LBP. Baseline psychosocial screening may serve as a method for identifying patients likely to benefit from this approach.
Construction of millimeter-scale vascularized engineered myocardial tissue using a mixed gel
Authors: Ke Ming , Xu Wenhui , Hao Yansha , Zheng Feiyang , Yang Guanyuan , Fan Yonghong , Wang Fangfang , Nie Zhiqiang , Zhu Chuhong
Published: December 2023

Engineering myocardium has shown great clinal potential for repairing permanent myocardial injury. However, the lack of perfusing blood vessels and difficulties in preparing a thick-engineered myocardium result in its limited clinical use. We prepared a mixed gel containing fibrin (5 mg/ml) and collagen I (0.2 mg/ml) and verified that human umbilical vein endothelial cells (HUVECs) and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could form microvascular lumens and myocardial cell clusters by harnessing the low-hardness and hyperelastic characteristics of fibrin. hiPSC-CMs and HUVECs in the mixed gel formed self-organized cell clusters, which were then cultured in different media using a three-phase approach. The successfully constructed vascularized engineered myocardial tissue had a spherical structure and final diameter of 1–2 mm. The tissue exhibited autonomous beats that occurred at a frequency similar to a normal human heart rate. The internal microvascular lumen could be maintained for 6 weeks and showed good results during preliminary surface re-vascularization in vitro and vascular remodeling in vivo. In summary, we propose a simple method for constructing vascularized engineered myocardial tissue, through phased cultivation that does not rely on high-end manufacturing equipment and cutting-edge preparation techniques. The constructed tissue has potential value for clinical use after preliminary evaluation.
Common ownership and creative destruction: evidence from US consumers
Authors: Aslan Hadiye
Published: December 2023

How does common ownership affect creative destruction? What are the underlying mechanisms? Do the effects of increased common ownership vary among different customer segments? Using product-level data, we show that, on average, firms with greater common ownership introduce new products at a faster rate and discontinue existing products at a similar pace. The observed economic impacts intensify over time, reflecting the gradual nature of knowledge spillovers and the learning curve. Subsequent to an increase in common ownership, portfolio firms tend to both add and drop products that are dissimilar to those of their rival firms, with the net effect of decreasing between-firm product dissimilarity. We also find that the effects are more relevant for product modules with greater technological likeness, lower barriers to market entry, and greater numbers of product market players. Product variety is substantially greater in product lines catering to higher-income households. Overall, the result highlights the procompetitive effects of increased common ownership.
Functional Connectome Hierarchy in Schizotypy and Its Associations With Expression of Schizophrenia-Related Genes
Authors: Dong Debo , Wang Yulin , Zhou Feng , Chang Xuebin , Qiu Jiang , Feng Tingyong , He Qinghua , Lei Xu , Chen Hong
Published: December 2023

Background and Hypothesis

Schizotypy has been conceptualized as a continuum of symptoms with marked genetic, neurobiological, and sensory-cognitive overlaps to schizophrenia. Hierarchical organization represents a general organizing principle for both the cortical connectome supporting sensation-to-cognition continuum and gene expression variability across the cortex. However, a mapping of connectome hierarchy to schizotypy remains to be established. Importantly, the underlying changes of the cortical connectome hierarchy that mechanistically link gene expressions to schizotypy are unclear.

Study Design

The present study applied novel connectome gradient on resting-state fMRI data from 1013 healthy young adults to investigate schizotypy-associated sensorimotor-to-transmodal connectome hierarchy and assessed its similarity with the connectome hierarchy of schizophrenia. Furthermore, normative and differential postmortem gene expression data were utilized to examine transcriptional profiles linked to schizotypy-associated connectome hierarchy.

Study Results

We found that schizotypy was associated with a compressed functional connectome hierarchy. Moreover, the pattern of schizotypy-related hierarchy exhibited a positive correlation with the connectome hierarchy observed in schizophrenia. This pattern was closely colocated with the expression of schizophrenia-related genes, with the correlated genes being enriched in transsynaptic, receptor signaling and calcium ion binding.

Conclusions

The compressed connectome hierarchy suggests diminished functional system differentiation, providing a novel and holistic system-level basis for various sensory-cognition deficits in schizotypy. Importantly, its linkage with schizophrenia-altered hierarchy and schizophrenia-related gene expression yields new insights into the neurobiological continuum of psychosis. It also provides mechanistic insight into how gene variation may drive alterations in functional hierarchy, mediating biological vulnerability of schizotypy to schizophrenia.
Making Gender Crises: State Newspapers and the Regulation of Gender Nonconformity in China
Authors: Zhou Xiaogao , Liu Songyin
Published: December 2023

Media coverage about transgender and gender nonconforming people both maintains and influences normative ideas about sex, gender, and sexuality. However, how state propaganda apparatus reifies these ideas through media and contributes to gender regulations remains underexplored, especially for state-dominated media systems. To bridge this gap, this article examines the media framing of gender nonconformity in China through a content analysis of 154 state-run newspaper articles from 1980 to 2021. Our analysis reveals that state newspapers introduce gender nonconformity into the purview of governance through two processes: 1) By pushing medicalized and socialization explanations for gender nonconformity, state newspapers consolidated two categories of gender nonconformity—intersex/transgender people and gender nonconforming youth. 2) State newspapers have developed two “gender crisis” frames that positioned the management of gender nonconformity at the heart of state governance and national development. Through this, gender nonconformity becomes legible for state institutions in criminal justice, medicine, marriage, education, and media. The findings contribute to the literature on media maintenance of the sex/gender/sexuality system by demonstrating the productive power of state-run media in shaping knowledge, discourse, and the regulation of gender nonconformity.
Paved with Good Intentions: Moral Evaluation of Volunteer Tourism as Social Action
Authors: Kahana Netta
Published: December 2023

This article explores how social actors account for their participation in a socially contested and criticized activity, while maintaining their moral self-worth. As a case study, the article focuses on volunteer tourism—a practice positioned at the intersection of economic inequality and global historical power relations, in which tourists combine volunteering in the Global South with vacationing. Despite public criticism, the practice is growing in popularity. Analyzing 48 in-depth interviews using theoretical ideas from the new cultural sociology of morality, I identify three predominant justifications invoked by volunteers to explain their actions. With each of these, interviewees assert the righteousness of their intentions, distancing themselves from the potentially negative outcomes of their actions—thus maintaining their moral self-worth, criticism of their actions notwithstanding. In articulating these claims, social actors express a distinct logic through which the moral evaluation of a social action is undertaken, emphasizing fundamental components of the action, referred to here as the intention and outcome propositions. The article highlights the importance of these interrelated propositions in understanding moral evaluations of an action, particularly in cases of possible moral devaluation.
Luxembourg tax updates
Authors: Fort Eric , Ajabli Bilal
Published: December 2023

This article aims at providing a holistic overview of Luxembourg’s tax framework applicable for individuals. Specifically, this article is divided into four sections. In the ‘Overview of the tax framework for individuals’ section, an overview of the Luxembourg income tax rules for each category of income will be given, after having defined the tax residency concept under Luxembourg tax law. We will also cover in the ‘Overview of the tax framework for individuals’ section other indirect taxes, such as gift and inheritance taxes. In the ‘Impatriate tax regime’ section, we will address the conditions required to benefit from the specific tax regime for qualifying international employees that have been introduced into Luxembourg tax lax. The ‘Profit-sharing premium’ section will address the profit-sharing bonus mechanism for employees, introduced to enhance the country’s attractiveness. Finally, the specific tax regime for carried interest, which has been implemented by the Law of 12 July 2013 in Luxembourg, will be covered.
Outcomes of Extracorporeal Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest Among Children With Noncardiac Illness Categories*
Authors: Loaec Morgann , Himebauch Adam S. , Reeder Ron , Alvey Jessica S. , Race Jonathan A. , Su Lillian , Lasa Javier J. , Slovis Julia C. , Raymond Tia T. , Coleman Ryan , Barney Bradley J. , Kilbaugh Todd J. , Topjian Alexis A. , Sutton Robert M. , Morgan Ryan W. ,   for the American Heart Association’s (AHA) Get With The Guidelines-Resuscitation (GWTG-R) Investigators
Published: December 2023

OBJECTIVES:

The objective of this study was to determine the association of the use of extracorporeal cardiopulmonary resuscitation (ECPR) with survival to hospital discharge in pediatric patients with a noncardiac illness category. A secondary objective was to report on trends in ECPR usage in this population for 20 years.

DESIGN:

Retrospective multicenter cohort study.

SETTING:

Hospitals contributing data to the American Heart Association’s Get With The Guidelines-Resuscitation registry between 2000 and 2021.

PATIENTS:

Children (<18 yr) with noncardiac illness category who received greater than or equal to 30 minutes of cardiopulmonary resuscitation (CPR) for in-hospital cardiac arrest.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Propensity score weighting balanced ECPR and conventional CPR (CCPR) groups on hospital and patient characteristics. Multivariable logistic regression incorporating these scores tested the association of ECPR with survival to discharge. A Bayesian logistic regression model estimated the probability of a positive effect from ECPR. A secondary analysis explored temporal trends in ECPR utilization. Of 875 patients, 159 received ECPR and 716 received CCPR. The median age was 1.0 [interquartile range: 0.2–7.0] year. Most patients (597/875; 68%) had a primary diagnosis of respiratory insufficiency. Median CPR duration was 45 [35–63] minutes. ECPR use increased over time (p < 0.001). We did not identify differences in survival to discharge between the ECPR group (21.4%) and the CCPR group (16.2%) in univariable analysis (p = 0.13) or propensity-weighted multivariable logistic regression (adjusted odds ratio 1.42 [95% CI, 0.84–2.40; p = 0.19]). The Bayesian model estimated an 85.1% posterior probability of a positive effect of ECPR on survival to discharge.

CONCLUSIONS:

ECPR usage increased substantially for the last 20 years. We failed to identify a significant association between ECPR and survival to hospital discharge, although a post hoc Bayesian analysis suggested a survival benefit (85% posterior probability).
Comparison of Outcomes of Facial Reanimation Between the Use of Cross-facial Nerve Graft and the Masseteric Nerve as the Donor Nerve for Reinnervation of Gracilis Muscle Flap Transfer
Authors: Liang Hongyu , Yang Zhe , Ma Ning , Wang Weixin , Li Yangqun
Published: December 2023

Background:

In patients with facial paralysis, the free functional gracilis muscle transfer is preferred for facial reanimation. The choice of an adequate motor nerve to innervate the transplanted gracilis muscle is one of the procedure’s key components. We present a comparative study between cross-facial nerve graft (CFNG) and masseteric nerve as donor nerves for reinnervated gracilis flap transfer in patients with complete facial paralysis.

Materlals and Methods:

Retrospective analysis was performed on all patients with complete facial paralysis who had a free functional gracilis muscle transfer for facial reanimation between January 2014 and December 2021. Only those who received gracilis transfer reinnervated by either CFNG or masseteric nerve were included in this study. The smile excursion and lip angle were measured for evaluating the outcomes postoperatively.

Results:

The inclusion criteria were met by a total of 21 free functional gracilis muscle transfers, of which 11 were innervated by CFNG and 10 by the masseteric nerve. Both surgical procedures resulted in a highly considerable smile excursion of the reanimated side and postoperative improvement of static or dynamic lip angle. Masseteric nerve coaptation led to greater smile excursion and more significant improvement of dynamic lip angle than CFNG.

Conclusions:

For patients who have complete facial paralysis, face reanimation can be successfully accomplished by free gracilis transfer reinnervated by the CFNG or the masseteric nerve. In particular, the masseteric nerve is a reliable choice for dynamic smile reanimation.
Customized Reconstruction of Lower Eyelid Defects
Authors: Kwon Hyeokjae , Song Bokeun , Ha Yooseok , Kim Sunje , Oh Sang-Ha , Seo Young-Joon , Song Seung Han
Published: December 2023

Background:

A lower eyelid defect is a loss of skin, muscle, and underlying structures that can occur due to trauma, malignant or benign tumors, burns, or other causes. The conventional surgical treatment of lower lid defects has several limitations, including visible scarring, narrowing of the eye, and ectropion. Here, we combined the use of a customized mid-face lift with a free mucochondral graft to overcome the disadvantages of existing methods.

Methods:

Forty patients underwent reconstructive surgery using a customized mid-face lift with or without a free mucochondral graft for a lower lid defect between April 2013 and October 2020. Patients were discharged shortly after surgery and were expected to visit the outpatient clinic periodically for 12 months.

Results:

The causes of lower eyelid defects were malignancy, trauma, foreign body granuloma, and other causes. Four patients reported complications, including 2 cases of chemosis, 1 case of a hematoma, and 1 case of corneal abrasion, who reportedly performed well after 2 weeks of conservative therapy. No patient required revision during the average follow-up period.

Conclusions:

Customized reconstruction demonstrated a better aesthetic reconstruction of the lower eyelid. This method represents a good option for reconstructing lower lid defects.
The accuracy of polygenic score models for anthropometric traits and Type II Diabetes in the Native Hawaiian Population
Authors: Lo Ying-Chu , Chan Tsz Fung , Jeon Soyoung , Maskarinec Gertraud , Taparra Kekoa , Nakatsuka Nathan , Yu Mingrui , Chen Chia-Yen , Lin Yen-Feng , Wilkens Lynne R. , Le Marchand Loic , Haiman Christopher A. , Chiang Charleston W.K.
Published: December 2023

Polygenic scores (PGS) are promising in stratifying individuals based on the genetic susceptibility to complex diseases or traits. However, the accuracy of PGS models, typically trained in European- or East Asian-ancestry populations, tend to perform poorly in other ethnic minority populations, and their accuracies have not been evaluated for Native Hawaiians. Using body mass index, height, and type-2 diabetes as examples of highly polygenic traits, we evaluated the prediction accuracies of PGS models in a large Native Hawaiian sample from the Multiethnic Cohort with up to 5,300 individuals. We evaluated both publicly available PGS models or genome-wide PGS models trained in this study using the largest available GWAS. We found evidence of lowered prediction accuracies for the PGS models in some cases, particularly for height. We also found that using the Native Hawaiian samples as an optimization cohort during training did not consistently improve PGS performance. Moreover, even the best performing PGS models among Native Hawaiians would have lowered prediction accuracy among the subset of individuals most enriched with Polynesian ancestry. Our findings indicate that factors such as admixture histories, sample size and diversity in GWAS can influence PGS performance for complex traits among Native Hawaiian samples. This study provides an initial survey of PGS performance among Native Hawaiians and exposes the current gaps and challenges associated with improving polygenic prediction models for underrepresented minority populations.
First-line chemotherapies administered before hematopoietic cell transplantation in children with acute leukemia: effect on the spermatogonial pool
Authors: Gille A.S. , Lenez L. , Vanhæsebrouck A. , Rivet-Danon D. , Lapoujade C. , Riou L. , Dalle J.H. , Yakouben K. , Peycelon M. , Fahd M. , Paye-Jaouen A. , Meyran D. , Leverger G. , Tabone M.D. , Boutroux H. , Irtan S. , Chenouf C. , Sibony M. , Chalas C. , Patrat C. , Wolf J.P. , Boissel N. , Fouchet P. , Poirot C. , Barraud-Lange V.
Published: December 2023

Approximately 20% of pediatric patients presenting with acute leukemia (AL) receive an allogeneic hematopoietic stem cell transplantation (HSCT) either in the first or subsequent complete remission. Survivors are exposed at adulthood to fertility impairment, which is one of the most worrisome long-term side effects of pre-HSCT myeloablative conditioning regimens, while conventional chemotherapy is associated with a low risk of infertility. Thus, fertility preservation is highly recommended in young patients before HSCT. Testicular tissue cryopreservation (TTC) is the only option offered to prepubertal or peripubertal patients, with the perspective of restoring fertility from the spermatogonia contained in the immature tissue. Our study presents the largest series published to date about the testicular tissue content of spermatogonia in young patients with AL after administration of first-line chemotherapies. It shows that non-alkylating chemotherapies administered before TTC do not significantly reduce the spermatogonial pool. Our work also confirms in a large population that CCD over 4 g/m² causes sharp depletion of the spermatogonial pool. This study provides new valuable information regarding the reproductive potential of testicular tissue collected before HSCT from children with AL previously exposed to first-line chemotherapies including alkylating agent or not.
A Retroactive Study on Factors Influencing the Efficacy of Treatment for Tuberculosis Patients with HIV: based on the data from 2010 to 2020 in Shanghai, China
Authors: Dong Chenyu , Zhang Renfang , Li Shenyang , Chen Jun , Liu Yunhe , Xia Xiaoqiong , Liu Gang , Shen Yinzhong , Liu Lei , Zeng Liyan
Published: December 2023

At present, the factors influencing Tuberculosis (TB) treatment effectiveness in HIV/TB co-infected patients need to be supported by more substantial real-world evidence. A retrospective study is conducted to fill the vacancy. 461 TB patients with HIV are defined as 742 samples according to each TB detection period. 7788 valid treatment records corresponding to 17 drug compositions for TB and 150 clinical indicators with more than 100 records are used to conduct data mining with consensus clustering, Fisher’s exact test, stratified analysis, and three modeling approaches, including logistic regression, support vector machine, and random forest. We find that A CD4+T cell count of 42 cells per μL may serve as a sensitive classification standard for the immune level to assist in evaluating or predicting the efficacy of TB (P=0.007); Rifabutin and levofloxacin alone or in combination may be more effective than other first- and second-line anti-TB agents in combination (P=0.037); Samples with low immune levels (CD4≦42) may be more resistant to first-line TB drugs (P=0.049); Age (P=0.015), bicarbonate radical (P=0.007), high-density lipoprotein cholesterol (P=0.026), pre-treatment CD8+T cell count (P=0.015, age<60, male), neutrophil percentage (P=0.033, age<60), rifabutin (P=0.010, age<60), and cycloserine (P=0.027, age<60) may influence the TB treatment effectiveness; More evidence is needed to support the relationship between pre-treatment clinical indicators or drug regimens and TB treatment effectiveness (The best AUC is 0.560∼0.763); The percentage of lymphocytes (P=0.028) can be used as an effective TB therapeutic target. These perspectives supplement knowledge in relevant clinical aspects.
Co designing a novel game for young people who have experienced adverse childhood experiences: Protocol
Authors: Butcher Isabelle , Fazel Mina , McCrone Paul , Krzywinska Tanya , Belinskiy Anton , Smith Lindsay , Ma Minhua , Pavarini Gabriela , Sansoy Harsimran , Mankee-Williams Anna , Teasdale Ben , Bhui Kamaldeep
Published: December 2023

Background

Adverse childhood experiences (ACEs) are associated with poorer mental health outcomes later in life. Research to date has focused on utilising qualitative and quantitative measures to understand possible mechanisms, and interventions for those who may have experienced ACEs.

Objectives

This study aims to co-design a novel digital game, in collaboration with youth and adult stakeholders, to engage 12-25-year olds in learning about the impact of ACEs and how to protect and promote mental health following ACE exposure. Additionally, this project aims to evaluate the feasibility and acceptability of such an intervention.

Methods

This study will adopt Experience Based Co- Design methods with adolescents aged between 12 and 24 living in England, and will involve adult stakeholders working in the public sector. We will then evaluate the feasibility and acceptability of the co-designed game on young people, and test its cost-effectiveness.

Conclusion

This project will enable an insight into the processes of co-designing a youth-informed public mental health game-based intervention and feasibility and acceptability of a serious game approach for adolescents aged between 12-24 years of age who may have experienced ACEs.

Strengths and limitations of this study

-

Adverse childhood experiences (ACEs) are associated with poorer mental health outcomes later in life. Research to date has primarily focused on quantitative and qualitative data to explore possible resources for young people. This study describes a novel digital game study for young people who may have experienced adversities.

-

The data on adverse childhood experiences has primarily on focused on urban and rural areas; this study seeks to recruit young people from rural, urban and coastal regions across England

-

This study is restricted to England, and whilst it is hoped the findings will be applicable to the U.K and more globally, the authors acknowledge the limitations of working with young people only in England

-

This study is one of a few studies that has sought to involve young people through the co design of a resource for young people who may have experienced adversities from initial conception of the idea to implementation of the game.
Ultrastructural, metabolic and genetic determinants of the acquisition of macrolide resistance byStreptococcus pneumoniae
Authors: Wu Xueqing , Alibayov Babek , Xiang Xi , Lattar Santiago M. , Sakai Fuminori , Medders Austin A. , Antezana Brenda , Keller Lance , Vidal Ana G. J. , Tzeng Yih-Ling , Robinson D. Ashley , Stephens David , Yu Yunsong , Vidal Jorge E.
Published: December 2023

Aim

Streptococcus pneumoniae(Spn) acquires genes for macrolide resistance, MEGA orermB, in the human host. These genes are carried either in the chromosome, or on integrative conjugative elements (ICEs). Here, we investigated molecular determinants of the acquisition of macrolide resistance.

Methods and Results

Whole genome analysis was conducted for 128 macrolide-resistant pneumococcal isolates to identify the presence of MEGA (44.5%, 57/128) orermB(100%), and recombination events in Tn916-related elements or in the locuscomCDEencoding competence genes. Confocal and electron microscopy studies demonstrated that, during the acquisition of macrolide resistance, pneumococcal strains formed clusters of varying size, with the largest aggregates having a median size of ∼1600 µm2. Remarkably, these pneumococcal aggregates comprise both encapsulated and nonencapsulated pneumococci, exhibited physical interaction, and spanned extracellular and intracellular compartments. We assessed the recombination frequency (rF) for the acquisition of macrolide resistance by a recipient D39 strain, from pneumococcal strains carrying MEGA (∼5.4 kb) in the chromone, or in large ICEs (>23 kb). Notably, the rF for the acquisition of MEGA, whether in the chromosome or carried on an ICE was similar. However, the rF adjusted to the acquisition of the full-length ICE (∼52 kb), compared to that of the capsule locus (∼23 kb) that is acquired by transformation, was three orders of magnitude higher. Finally, metabolomics studies revealed a link between the acquisition of ICE and the metabolic pathways involving nicotinic acid and sucrose.

Conclusions

Extracellular and intracellular pneumococcal clusters facilitate the acquisition of full-length ICE at a rF higher than that of typical transformation events, involving distinct metabolic changes that present potential targets for interventions.
Psychometric validation and clinical correlates of an experiential foraging task
Authors: McInnes Aaron N. , Sullivan Christi R. P. , MacDonald Angus W. , Widge Alik S.
Published: December 2023

Measuring the function of decision-making systems is a central goal of computational psychiatry. Individual measures of decisional function could be used to describe neurocognitive profiles that underpin psychopathology and offer insights into deficits that are shared across traditional diagnostic classes. However, there are few demonstrably reliable and mechanistically relevant metrics of decision making that can accurately capture the complex overlapping domains of cognition whilst also quantifying the heterogeneity of function between individuals. The WebSurf task is a reverse-translational human experiential foraging paradigm which indexes naturalistic and clinically relevant decision-making. To determine its potential clinical utility, we examined the psychometric properties and clinical correlates of behavioural parameters extracted from WebSurf in an initial exploratory experiment and a pre-registered validation experiment. Behaviour was stable over repeated administrations of the task, as were individual differences. The ability to measure decision making consistently supports the potential utility of the task in predicting an individual’s propensity for response to psychiatric treatment, in evaluating clinical change during treatment, and in defining neurocognitive profiles that relate to psychopathology. Specific aspects of WebSurf behaviour also correlate with anhedonic and externalising symptoms. Importantly, these behavioural parameters may measure dimensions of psychological variance that are not captured by traditional rating scales. WebSurf and related paradigms might therefore be useful platforms for computational approaches to precision psychiatry.
Cell-Free Optimized Production of Protoporphyrin IX
Authors: Garcia David C. , Davies John P. , Rhea Katherine , Lee Marilyn , Lux Matthew W.
Published: December 2023

Background

The asymmetric and aromatic structures of porphyrins enable semiconducting properties allowing them to absorb light to initiate complex photocatalytic activity. These properties coupled with biological origins have garnered these molecules and their derivatives wide interest as a biotechnological platform. However, porphyrin production in cells is challenging due to the limited titer, long production timescales, and difficult purification.

Results

A cell-free metabolic engineering platform was constructed to produce protoporphyrin IX (PPIX) fromE. colicrude extracts. Using acoustic liquid-handling, design of experiments for high-throughput buffer optimization and co-culturing techniques for extract production, our cell-free reactions effectively produced 0.109 mg/mL quantities of porphyrins.

Conclusions

The use of cell-free metabolic engineering as a bioproduction platform could improve the production of toxic or inefficient biomolecules such as PPIX. The engineering strategies including DOE and co-culturing applied in this study provide a roadmap towards increasing the scale of cell-free metabolic engineering by elucidating batch to batch variability, as well as the need for batch specific optimization of reaction conditions.
Improving the power of drug toxicity measurements by quantitative nuclei imaging
Authors: Mikheeva Alesya M. , Bogomolov Mikhail A. , Sementsov Mikhail V. , Spirin Pavel V. , Prassolov Vladimir S. , Lebedev Timofey
Published: December 2023

Imaging-based anticancer drug screens are becoming more prevalent due to development of automated fluorescent microscopes and imaging stations, as well as rapid advancements in imaging processing software. Automated cell imaging provides many benefits such as their ability to provide high-content data, modularity, dynamics recording and the fact that imaging is the most direct way to access cell viability and cell proliferation. However, currently most publicly available large-scale anticancer drugs screens, such as GDSC, CTRP and NCI-60, provide cell viability data measured by assays based on colorimetric or luminometric measurements of NADH or ATP levels. Although such datasets provide valuable data, it is unclear how well drug toxicity measurements can be integrated with imaging data. Here we explored the relations between drug toxicity data obtained by XTT assay, two quantitative nuclei imaging methods and trypan blue dye exclusion assay using a set of four cancer cell lines with different morphologies and 30 drugs with different mechanisms of action. We show that imaging-based approaches provide high accuracy and the differences between results obtained by different methods highly depend on drug mechanism of action. Selecting AUC metrics over IC50 or comparing data where significantly drugs reduced cell numbers noticeably improves consistency between methods. Using automated cell segmentation analysis and data-driven approach we show that XTT assay produces unreliable data for cell cycle and DNA repair inhibitors due induced cell size growth and increase in mitochondria activity. We also explored several benefits of image-based analysis such as ability to monitor cell number dynamics, dissect changes in mitochondria activity from cell proliferation, and ability to identify chromatin remodeling drugs. Finally, we will provide a web tool that allows comparing results obtained by different methods.
Prognostic relevance of correlated co-expression of coding and noncoding RNAs in cervical cancers
Authors: Ghosh Abhisikta , Sinha Abarna , Ghosh Arnab , Roy Somrita , Mallick Sumana , Kumar Vinoth , Mathai Sonia , Bhaumik Jaydip , Mukhopadhyay Asima , Sen Saugata , Chandra Aditi , Maitra Arindam , Biswas Nidhan K. , Majumder Partha P. , Sengupta Sharmila
Published: December 2023

Human papillomavirus (HPV) drives cervical cancer (CaCx) pathogenesis and viral oncoproteins jeopardize global gene expression in such cancers. We aimed to identify differentially expressed coding (DEcGs) and long noncoding (sense intronic and Natural Antisense Transcripts) RNA genes (DElncGs) in HPV16-positive CaCx patients (N=44) compared to HPV-negative normal individuals (N=34). Thereby, employing strand-specific RNA-seq, we determined the relationships between DEcGs and DElncGs and their clinical implications. Gene set enrichment and protein-protein interaction analyses of DEcGs revealed enrichment of processes crucial for abortive virus life cycle and cancer progression. The DEcGs formed 16 gene clusters, portraying cancer-related functions. We recorded significantly correlated co-expression of 79 DElncGs with DEcGs at proximal genomic loci, and 24 such pairs portrayed significantly altered correlation coefficients among patients, compared to normal individuals. Of these, 6 DEcGs belonged to 5 gene clusters, one of which was survival-associated. Out of the 24 correlated DEcG: DElncG pairs, 3 pairs were identified, where expression of both members was significantly associated with patient overall survival. Besides being prognostically relevant, disruption of the significant correlative relationships of such gene pairs in CaCx bears immense potential for patient-targeted therapy.Graphical Abstract:

A schematic representation of the analyses undertaken to draw insights on the biological relevance of joint analysis of co-expressed and significantly correlated DElncGs and DEcGs considering the ncNATs and sense intronic DElncGs, in HPV16-positive CaCx patients compared with HPV-negative normal individuals.
Who wreaks more havoc? Gender and the detrimental effect of abusive supervision on interpersonal deviance
Authors: Wang Haizhen , Zhang Ruoyong
Published: December 2023

Purpose

Abusive supervision provokes subordinates’ interpersonal deviant behavior. It is, therefore, essential to explore the contingent factors of this relationship. Drawing upon gender role theory, this study aims to explore how subordinate and leader genders moderate the relationship between abusive supervision and subordinate interpersonal deviance. Furthermore, this study posits a three-way interaction effect of abusive supervision with leader and subordinate genders on interpersonal deviance.

Design/methodology/approach

Multisource survey data were collected from 45 supervisors and 170 subordinates in eight companies in China. The data were analyzed using the PROCESS macro in SPSS.

Findings

The results showed that the positive relationship between abusive supervision and interpersonal deviance was stronger among female leaders than male leaders. Furthermore, the authors found a three-way interaction effect between abusive supervision and leader and subordinate genders on subordinates’ interpersonal deviance. Compared with female subordinates, male subordinates engaged in significantly more interpersonal deviance when experiencing abusive supervision from a female leader than from a male leader.

Originality/value

The authors reveal that gender differences exist in the effect of abusive supervision on subordinates’ interpersonal deviant behavior. Furthermore, the authors demonstrate that subordinate and leader genders jointly influence the effect of abusive supervision. Finally, the findings extend the literature on gender’s moderating effects from constructive and neutral leader behaviors to destructive leader behaviors.
Are firms more concerned about analysts’ earnings forecasts after the split-share structure reform? Evidence from China
Authors: Xi Xunzhuo , Chen Can , Huang Rong , Tang Feng
Published: December 2023

Purpose

This study aims to examine whether Chinese firms increase their concerns about analysts’ earnings forecasts following the split-share structure reform (SSR) in 2005, which removed trading restrictions on approximately 70% of the shares of listed firms.

Design/methodology/approach

Using data from 2002 to 2019, the authors empirically test the association between meeting or beating analysts’ earnings expectations and the implementation of SSR.

Findings

The authors find that firms are more inclined to meet analysts’ earnings expectations after the introduction of SSR. Further analysis shows that firms guide analysts to walk their forecasts down by manipulating third-quarter earnings, suggesting enhanced value relevance between analysts’ forecasts and third-quarter earnings management in the postreform period.

Practical implications

The findings reveal an undesirable side effect of SSR and suggest that policymakers and regulators should consider and carefully manage the complex relationships between firms and analysts.

Originality/value

In contrast to prior studies that predominantly focus on the positive effects of the reform, this study reveals the side effects of SSR and provides new evidence on the mechanisms of meeting or beating analysts’ earnings expectations.