bluuebunny/crossref_metadata_2025 huggingface dataset:
Increase of avian Plasmodium circumflexum prevalence, but not of other malaria parasites and related haemosporidians in northern Europe during the past 40 years
Authors: Valkiūnas Gediminas , Duc Mélanie , Iezhova Tatjana A.
Published: March 2022

Background

Malaria is a health problem not only in human and veterinary medicine, but also in wildlife. Several theoretical studies have suggested that avian malaria transmission might be increasing in Europe. However, there are few direct empirical observations. Research on the distribution of avian haemosporidian parasites was initiated around the Curonian Lagoon, Europe in 1976 and continues since. This has provided an opportunity to compare the prevalence and diversity of avian malaria parasites (genus Plasmodium) and related haemosporidians (genera Haemoproteus and Leucocytozoon) in the same bird species using similar methodology but examined in two groups 40 years apart. This study aimed to describe and discuss the available data on this subject.

Methods

Prevalence and diversity of haemosporidians was compared in two passeriform bird groups, which consisted of the same species that were sampled on the coast of the Curonian Lagoon (Russia, Lithuania) during the same season (September) in 1978–1983 (bird Group 1) and 2020 (bird Group 2). Blood films of the European robin, Coal tit, Great tit, Eurasian wren, and Eurasian jay were screened by microscopic examination. Parasites were identified using morphological characters of blood stages. PCR-based methods were applied to determine genetic lineages of the parasites found in birds of Group 2.

Results

No difference was discernible in the prevalence or diversity of haemosporidian parasites belonging to Haemoproteus, Leucocytozoon, Plasmodium (Haemamoeba) and Plasmodium (Novyella) between birds of Groups 1 and 2. This indicates a similar rate of transmission and relatively stable epidemiological situation in regard of these infections during the past 40 years. The prevalence of only one malaria parasite species, Plasmodium (Giovannolaia) circumflexum, increased remarkably, but only in Coal tit, Great tit, and Eurasian wren, with no significant prevalence change in European robin and Eurasian jay.

Conclusion

Plasmodium circumflexum is spreading and seems to be a new invasive avian malaria pathogen in countries with cold climates. The exceptionally high prevalence of P. circumflexum in birds breeding in relatively close-nests suggests an important role of the nesting biology related to bird-vector interaction in this pathogen transmission. The epidemiological situation seems to be relatively stable in regard of other studied avian hosts and haemosporidian parasites in northern Europe.
Endometriosis does not seem to be an influencing factor of hypertensive disorders of pregnancy in IVF / ICSI cycles
Authors: Lee Pingyin , Zhou Canquan , Li Yubin
Published: March 2022

Introduction

To evaluate whether the incidence of hypertensive disorders of pregnancy (HDP) in pregnant women was related to endometriosis (EM), ovulation and embryo vitrification technology.

Methods

A retrospective cohort study was conducted on the clinical data of 3674 women who were treated with IVF / ICSI in the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University and maintained clinical pregnancy for more than 20 weeks. All pregnancies were followed up until the end of pregnancy. The follow-up consisted of recording the course of pregnancy, pregnancy complications, and basic situation of newborns.

Results

Compared with NC-FET without EM, HRT-FET without EM was found to have a higher incidence of HDP during pregnancy (2.7% V.S. 6.1%, P<0.001); however, no significant difference was found in the incidence of HDP between NC-FET and HRT-FET combined with EM (4.0% V.S. 5.7%, P>0.05). In total frozen-thawed embryo transfer (total-FET), the incidence of HDP in the HRT cycle without ovulation (HRT-FET) was observed to be higher than that in the NC cycle with ovulation (NC-FET) (2.8% V.S. 6.1%, P<0.001). In patients with EM, no significant difference was found in the incidence of HDP between fresh ET and NC-FET (1.2% V.S. 4.0%, P>0.05).

Conclusion

EM does not seem to have an effect on the occurrence of HDP in assisted reproductive technology. During the FET cycle, the formation of the corpus luteum may play a protective role in the occurrence and development of HDP. Potential damage to the embryo caused by cryopreservation seems to have no effect on the occurrence of HDP.
Sugar-sweetened beverage tax implementation processes: results of a scoping review
Authors: Forberger Sarah , Reisch Lucia , Meshkovska Biljana , Lobczowska Karolina , Scheller Daniel Alexander , Wendt Janine , Christianson Lara , Frense Jennifer , Steinacker Jürgen Michael , Luszczynska Aleksandra , Zeeb Hajo ,   on behalf of the PEN Consortium
Published: March 2022

Taxing sugar-sweetened beverages (SSB) is seen as a win–win situation for governments. It is argued that SSB taxes are relatively easy to implement from a practical perspective compared to for example other nutrition policies. However, the implementation of SSB taxation laws does not happen by itself. Therefore, this work examines implementation processes for SSB taxation in terms of (1) pre-implementation context, (2) taxation instruments used and (3) interactions in the implementation process. Ten databases and grey literature were systematically searched for studies reporting on SSB taxation implementation processes up to February 2020. All studies (N = 1248) were screened independently by two reviewers according to predefined criteria. The selection of variables to be extracted was based on the policy cycle heuristic and informed by intervention implementation research. Information on the process of implementing SSB taxation is limited. Only six cases based on three publications were identified, indicating a gap in this research area. SSB taxation implementation was accomplished by hiring a subcontractor for the implementation or using pre-existing tax collection structures. Political and public support within the implementation process seems to be supportive for the city of Berkeley and for Portugal but was not reported for the Pacific Islands. However, the existing data are very limited, and further research on SSB taxation implementation processes is needed to determine whether the aim of the policy and the envisaged outcome are linked in practice.

Registration The protocol was registered with the Open Science Framework (OSF) (osf.io/7w84q/)
Rest-activity profiles among U.S. adults in a nationally representative sample: a functional principal component analysis
Authors: Xiao Qian , Lu Jiachen , Zeitzer Jamie M. , Matthews Charles E. , Saint-Maurice Pedro F. , Bauer Cici
Published: March 2022

Background

The 24-h rest and activity behaviors (i.e., physical activity, sedentary behaviors and sleep) are fundamental human behaviors essential to health and well-being. Functional principal component analysis (fPCA) is a flexible approach for characterizing rest-activity rhythms and does not rely on a priori assumptions about the activity shape. The objective of our study is to apply fPCA to a nationally representative sample of American adults to characterize variations in the 24-h rest-activity pattern, determine how the pattern differs according to demographic, socioeconomic and work characteristics, and examine its associations with general health status.

Methods

The current analysis used data from adults 25 or older in the National Health and Nutrition Examination Survey (NHANES, 2011–2014). Using 7-day 24-h actigraphy recordings, we applied fPCA to derive profiles for overall, weekday and weekend rest-activity patterns. We examined the association between each rest-activity profile in relation to age, gender, race/ethnicity, education, income and working status using multiple linear regression. We also used multiple logistic regression to determine the relationship between each rest-activity profile and the likelihood of reporting poor or fair health.

Results

We identified four distinct profiles (i.e., high amplitude, early rise, prolonged activity window, biphasic pattern) that together accounted for 86.8% of total variation in the study sample. We identified numerous associations between each rest-activity profile and multiple sociodemographic characteristics. We also found evidence suggesting the associations differed between weekdays and weekends. Finally, we reported that the rest-activity profiles were associated with self-rated health.

Conclusions

Our study provided evidence suggesting that rest-activity patterns in human populations are shaped by multiple demographic, socioeconomic and work factors, and are correlated with health status.
Supernumerary derivative 22 chromosome resulting from novel constitutional non-Robertsonian translocation: t(20;22)—Case Report
Authors: Manju H. C. , Bevinakoppamath Supriya , Bhat Deepa , Prashant Akila , Kadandale Jayaram S. , Sairam P. V. V. Gowri
Published: March 2022

Background

Maternal non-Robertsonian translocation-t(20;22)(q13;q11.2) between chromosomes 20 and 22resulting in an additional complex small supernumerary marker chromosome as derivative (22)inherited to the proband is not been reported yet.

Case presentation

A 4 years old boy with a history of developmental delay, low set ears, and facial dysmorphism was presented to the genetic clinic. Periauricular pit, downward slanting eyes, medially flared eyebrows, downturned mouth corners, and micrognathia were observed. He had congenital heart defect with atrial septal defect (ASD), ventricular septal defect (VSD), and central nervous system (CNS) anomalies with the gross cranium. Karyotype analysis, Fluorescent in-situ hybridization analysis (FISH), and Chromosomal microarray analysis (CMA) were used to determine the chromosomal origin and segmental composition of the derivative 22 chromosome. Karyotype and FISH analyses were performed to confirm the presence of a supernumerary chromosome, and Microarray analysis was performed to rule out copy number variations in the proband's 22q11.2q12 band point. The probands' karyotype revealed the inherited der(22)t(20;22)(q13;q11.2)dmat. Parental karyotype confirmed the mother as the carrier, with balanced non-Robertsonian translocation-46,XX,t(20;22)(q13;q11.2).

Conclusion

The mother had a non-Robertsonian translocation t(20;22)(q13;q11.2) between chromosomes 20 and 22, which resulted in Emanuel syndrome in the proband. The most plausible explanation is 3:1 meiotic malsegregation, which results in the child inheriting derivative chromosome. The parental karyotype study aided in identifying the carrier of the supernumerary der(22), allowing future pregnancies with abnormal offspring to be avoided.
Brain region networks for the assimilation of new associative memory into a schema
Authors: Takeuchi Tomonori , Tamura Makoto , Tse Dorothy , Kajii Yasushi , Fernández Guillén , Morris Richard G. M.
Published: March 2022

Alterations in long-range functional connectivity between distinct brain regions are thought to contribute to the encoding of memory. However, little is known about how the activation of an existing network of neocortical and hippocampal regions might support the assimilation of relevant new information into the preexisting knowledge structure or ‘schema’. Using functional mapping for expression of plasticity-related immediate early gene products, we sought to identify the long-range functional network of paired-associate memory, and the encoding and assimilation of relevant new paired-associates. Correlational and clustering analyses for expression of immediate early gene products revealed that midline neocortical-hippocampal connectivity is strongly associated with successful memory encoding of new paired-associates against the backdrop of the schema, compared to both (1) unsuccessful memory encoding of new paired-associates that are not relevant to the schema, and (2) the mere retrieval of the previously learned schema. These findings suggest that the certain midline neocortical and hippocampal networks support the assimilation of newly encoded associative memories into a relevant schema.
Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy
Authors: Jiang Yangfu , Zhang Hongying , Wang Jiao , Liu Yongliang , Luo Ting , Hua Hui
Published: March 2022

Cancer microenvironment is critical for tumorigenesis and cancer progression. The extracellular matrix (ECM) interacts with tumor and stromal cells to promote cancer cells proliferation, migration, invasion, angiogenesis and immune evasion. Both ECM itself and ECM stiffening-induced mechanical stimuli may activate cell membrane receptors and mechanosensors such as integrin, Piezo1 and TRPV4, thereby modulating the malignant phenotype of tumor and stromal cells. A better understanding of how ECM stiffness regulates tumor progression will contribute to the development of new therapeutics. The rapidly expanding evidence in this research area suggests that the regulators and effectors of ECM stiffness represent potential therapeutic targets for cancer. This review summarizes recent work on the regulation of ECM stiffness in cancer, the effects of ECM stiffness on tumor progression, cancer immunity and drug resistance. We also discuss the potential targets that may be druggable to intervene ECM stiffness and tumor progression. Based on these advances, future efforts can be made to develop more effective and safe drugs to interrupt ECM stiffness-induced oncogenic signaling, cancer progression and drug resistance.
OVOL2 impairs RHO GTPase signaling to restrain mitosis and aggressiveness of Anaplastic Thyroid Cancer
Authors: Gugnoni Mila , Manzotti Gloria , Vitale Emanuele , Sauta Elisabetta , Torricelli Federica , Reggiani Francesca , Pistoni Mariaelena , Piana Simonetta , Ciarrocchi Alessia
Published: March 2022

Background

Anaplastic Thyroid Cancer (ATC) is an undifferentiated and aggressive tumor that often originates from well-Differentiated Thyroid Carcinoma (DTC) through a trans-differentiation process. Epithelial-to-Mesenchymal Transition (EMT) is recognized as one of the major players of this process. OVOL2 is a transcription factor (TF) that promotes epithelial differentiation and restrains EMT during embryonic development. OVOL2 loss in some types of cancers is linked to aggressiveness and poor prognosis. Here, we aim to clarify the unexplored role of OVOL2 in ATC.

Methods

Gene expression analysis in thyroid cancer patients and cell lines showed that OVOL2 is mainly associated with epithelial features and its expression is deeply impaired in ATC. To assess OVOL2 function, we established an OVOL2-overexpression model in ATC cell lines and evaluated its effects by analyzing gene expression, proliferation, invasion and migration abilities, cell cycle, specific protein localization through immunofluorescence staining. RNA-seq profiling showed that OVOL2 controls a complex network of genes converging on cell cycle and mitosis regulation and Chromatin Immunoprecipitation identified new OVOL2 target genes.

Results

Coherently with its reported function, OVOL2 re-expression restrained EMT and aggressiveness in ATC cells. Unexpectedly, we observed that it caused G2/M block, a consequent reduction in cell proliferation and an increase in cell death. This phenotype was associated to generalized abnormalities in the mitotic spindle structure and cytoskeletal organization. By RNA-seq experiments, we showed that many pathways related to cytoskeleton and migration, cell cycle and mitosis are profoundly affected by OVOL2 expression, in particular the RHO-GTPase pathway resulted as the most interesting. We demonstrated that RHO GTPase pathway is the central hub of OVOL2-mediated program in ATC and that OVOL2 transcriptionally inhibits RhoU and RhoJ. Silencing of RhoU recapitulated the OVOL2-driven phenotype pointing to this protein as a crucial target of OVOL2 in ATC.

Conclusions

Collectively, these data describe the role of OVOL2 in ATC and uncover a novel function of this TF in inhibiting the RHO GTPase pathway interlacing its effects on EMT, cytoskeleton dynamics and mitosis.
Physical separation of haplotypes in dikaryons allows benchmarking of phasing accuracy in Nanopore and HiFi assemblies with Hi-C data
Authors: Duan Hongyu , Jones Ashley W. , Hewitt Tim , Mackenzie Amy , Hu Yiheng , Sharp Anna , Lewis David , Mago Rohit , Upadhyaya Narayana M. , Rathjen John P. , Stone Eric A. , Schwessinger Benjamin , Figueroa Melania , Dodds Peter N. , Periyannan Sambasivam , Sperschneider Jana
Published: March 2022

Background

Most animals and plants have more than one set of chromosomes and package these haplotypes into a single nucleus within each cell. In contrast, many fungal species carry multiple haploid nuclei per cell. Rust fungi are such species with two nuclei (karyons) that contain a full set of haploid chromosomes each. The physical separation of haplotypes in dikaryons means that, unlike in diploids, Hi-C chromatin contacts between haplotypes are false-positive signals.

Results

We generate the first chromosome-scale, fully-phased assembly for the dikaryotic leaf rust fungus Puccinia triticina and compare Nanopore MinION and PacBio HiFi sequence-based assemblies. We show that false-positive Hi-C contacts between haplotypes are predominantly caused by phase switches rather than by collapsed regions or Hi-C read mis-mappings. We introduce a method for phasing of dikaryotic genomes into the two haplotypes using Hi-C contact graphs, including a phase switch correction step. In the HiFi assembly, relatively few phase switches occur, and these are predominantly located at haplotig boundaries and can be readily corrected. In contrast, phase switches are widespread throughout the Nanopore assembly. We show that haploid genome read coverage of 30–40 times using HiFi sequencing is required for phasing of the leaf rust genome, with 0.7% heterozygosity, and that HiFi sequencing resolves genomic regions with low heterozygosity that are otherwise collapsed in the Nanopore assembly.

Conclusions

This first Hi-C based phasing pipeline for dikaryons and comparison of long-read sequencing technologies will inform future genome assembly and haplotype phasing projects in other non-haploid organisms.
Fragment-based virtual screening discovers potential new Plasmodium PI4KIIIβ ligands
Authors: Ibezim Akachukwu , Madukaife Mbanefo S. , Osigwe Sochi C. , Engel Nadja , Karuppasamy Ramanathan , Ntie-Kang Fidele
Published: March 2022

Type III beta phosphatidylinositol 4-kinase (PI4KIIIβ) is the only clinically validated drug target in Plasmodium kinases and therefore a critical target in developing novel drugs for malaria. Current PI4KIIIβ inhibitors have solubility and off-target problems. Here we set out to identify new Plasmodium PI4K ligands that could serve as leads for the development of new antimalarial drugs by building a PPI4K homology model since there was no available three-dimensional structure of PfPI4K and virtually screened a small library of ~ 22 000 fragments against it. Sixteen compounds from the fragment-based virtual screening (FBVS) were selected based on ≤ − 9.0 kcal/mol binding free energy cut-off value. These were subjected to similarity and sub-structure searching after they had passed PAINS screening and the obtained derivatives showed improved binding affinity for PfPI4K (− 10.00 to − 13.80 kcal/mol). Moreover, binding hypothesis of the top-scoring compound (31) was confirmed in a 100 ns molecular dynamics simulation and its binding pose retrieved after the system had converged at about 10 ns into the evolution was described to lay foundation for a rationale chemical-modification to optimize binding to PfPI4K. Overall, compound 31 appears to be a viable starting point for the development of PPI4K inhibitors with antimalarial activity.
The effect of mitochondrial fusion on chondrogenic differentiation of cartilage progenitor/stem cells via Notch2 signal pathway
Authors: Moqbel Safwat Adel Abdo , Zeng Rong , Ma Diana , Xu Langhai , Lin Changjian , He Yuzhe , Ma Chiyuan , Xu Kai , Ran Jisheng , Jiang Lifeng , Wu Lidong
Published: March 2022

Background

Osteoarthritis (OA) is a debilitating disease that inflicts intractable pain, a major problem that humanity faces, especially in aging populations. Stem cells have been used in the treatment of many chronic diseases, including OA. Cartilage progenitor/stem cells (CPSCs) are a type of stem cells with the ability to self- renew and differentiate. They hold a promising future for the understanding of the progression of OA and for its treatment. Previous studies have reported the relationship between mitochondrial dynamics and mesenchymal stem cell (MSC) proliferation, differentiation and aging. Mitochondrial dynamic and morphology change during stem cell differentiation.

Methods

This study was performed to access the relationship between mitochondrial dynamics and chondrogenic differentiation of CPSCs. Mitochondrial fusion and fission levels were measured during the chondrogenic differentiation process of CPSCs. After that, we used mitochondrial fusion promoter to induce fusion in CPSCs and then the chondrogenic markers were measured. Transmission electron microscopy (TEM) and confocal microscopy were used to capture the mass and fusion status of mitochondria. Lentiviruses were used to detect the role of mitofusin 2 (Mfn2) in CPSC chondrogenic differentiation. In vivo, Mfn2 was over-expressed in sheets of rat CPSCs, which were then injected intra-articularly into the knees of rats.

Results

Mitochondrial fusion markers were upregulated during the chondrogenic induction process of CPSCs. The mass of mitochondria was higher in differentiated CPSC, and the fusion status was obvious relative to un-differentiated CPSC. Chondrogenesis of CPSCs was upregulated with the induction by mitochondrial fusion promoter. Mfn2 over-expression significantly increased chondrocyte-specific gene expression and reversed OA through NOTCH2 signal pathway.

Conclusions

Our study demonstrated that the mitochondrial fusion promotes chondrogenesis differentiation of CPSCs. Mfn2 accelerates the chondrogenesis differentiation of CPSCs through Notch2. In vivo, Mfn2-OE in sheets of rCPSCs ameliorated OA in the rat model.
Mixed-type data generation method based on generative adversarial networks
Authors: Wei Ning , Wang Longzhi , Chen Guanhua , Wu Yirong , Sun Shunfa , Chen Peng
Published: March 2022

Data-driven based deep learing has become a key research direction in the field of artificial intelligence. Abundant training data is a guarantee for building efficient and accurate models. However, due to the privacy protection policy, research institutions are often limited to obtain a large number of training data, which would lead to a lack of training sets circumstance. In this paper, a mixed-type data generation model based on generative adversarial networks is proposed to synthesize fake data that have the same distribution with the real data, so as to supplement the real data and increase the number of available samples. The model first pre-trains the autoencoder which maps given dataset into a low-dimensional continuous space. Then, the generator constructed in the low-dimension space is obtained by training it adversarially with discriminator constructed in the original space. Since the constructed discriminator not only consider the loss of the continuous attributes but also the labeled attributes, the generator nets formed by the generator and the decoder can effectively learn the intrinsic distribution of the mixed data. We evaluate the proposed method both in the independent distribution of the attribute and in the relationship of the attributes, and the experiment results show that the proposed generate method has a better performance in preserve the intrinsic distribution compared with other generation algorithms based on deep learning.
Piperonal synthase from black pepper (Piper nigrum) synthesizes a phenolic aroma compound, piperonal, as a CoA-independent catalysis
Authors: Jin Zhehao , Ro Dae-Kyun , Kim Soo-Un , Kwon Moonhyuk
Published: March 2022

Piperonal is a simple aromatic aldehyde compound with a characteristic cherry-like aroma and has been widely used in the flavor and fragrance industries. Despite piperonal being an important aroma in black pepper (Piper nigrum), its biosynthesis remains unknown. In this study, the bioinformatic analysis of the P. nigrum transcriptome identified a novel hydratase-lyase, displaying 72% amino acid identity with vanillin synthase, a member of the cysteine proteinase family. In in vivo substrate-feeding and in vitro enzyme assays, the hydratase-lyase catalyzed a side-chain cleavage of 3,4-methylenedioxycinnamic acid (3,4-MDCA) to produce 3,4-methylenedioxybenzaldehyde (piperonal) and thus was named piperonal synthase (PnPNS). The optimal pH for PnPNS activity was 7.0, and showed a Km of 317.2 μM and a kcat of 2.7 s−1. The enzyme was most highly expressed in the leaves, followed by the fruit. This characterization allows for the implementation of PnPNS in various microbial platforms for the biological production of piperonal.
Trends in platelet count among cancer patients
Authors: Giannakeas Vasily
Published: March 2022

An elevated platelet count has been associated with an increased incidence of cancer and poor survival for many cancer types. In this study, platelet levels were captured among cancer patients in the 2 years prior to and following a cancer diagnosis. I investigated if the trends in platelet count differ between patients that died or did not die from their cancer. For many cancer types, including colon, lung, ovary, and stomach, platelet counts rose as they approached the date of diagnosis. Patients that died from their cancer within 3 years of diagnosis had a higher peak platelet count than those who survived. Following diagnosis, platelet count was elevated among patients that died from their cancer as compared to patients who survived. An elevated platelet count could potentially indicate the presence of an occult cancer or be used as a prognostic measure for cancer-specific survival.
Exploring associations between positive and negative valanced parental comments about adolescents’ bodies and eating and eating problems: a community study
Authors: Dahill Lucy M. , Morrison Natalie M. V. , Mannan Haider , Mitchison Deborah , Touyz Stephen , Bussey Kay , Trompeter Nora , Hay Phillipa
Published: March 2022

Background

Adolescence is a time of rapid emotional and physical development when foundational self-concepts (including beliefs about one’s weight and shape) are established. Parents are key influencers of adolescent beliefs and behaviours. This study aimed to investigate associations between perceived positive and negative parental comments on weight/shape and eating, with sons’ and daughters’ psychological distress and eating disorder cognitions (EDCs).

Methods

A representative mixed-sex sample of 2204 Australian adolescents (12–19 years) from the EveryBODY Study completed an online survey exploring eating behaviours, psychological wellbeing and experiences of parental comments regarding weight, shape and eating behaviours.

Results

Correlation analyses revealed that adolescents’ reports of perceived positive parental comments on shape/weight were significantly associated with lower psychological distress and EDCs only for daughters. All perceived negative parental comments on shape/weight or eating were associated with greater psychological distress and EDCs for both sons and daughters. In the final model of the regression analysis, only perceived parental negative shape/weight and maternal negative eating comments, adolescent stage and biological sex were significantly associated with EDCs. When known contributors such as BMI percentile and psychological distress were included in the regression model, adolescent stage and perceived negative paternal comments were no longer significantly associated with EDCs.

Conclusions

Overall, results show perceived negative comments were associated with poorer adolescent mental health, both their specific EDCs and general distress. Findings highlight the importance of raising awareness of potential negative impacts within family systems of comments around weight/shape and eating in these key formative years.

Trial Registration The study was approved by the Macquarie University Human Research Ethics Committee (HREC 5201600312) and the New South Wales Department of Education.
Human induced-T-to-natural killer cells have potent anti-tumour activities
Authors: Jiang Zhiwu , Qin Le , Tang Yuou , Liao Rui , Shi Jingxuan , He Bingjia , Li Shanglin , Zheng Diwei , Cui Yuanbin , Wu Qiting , Long Youguo , Yao Yao , Wei Zhihui , Hong Qilan , Wu Yi , Mai Yuanbang , Gou Shixue , Li Xiaoping , Weinkove Robert , Norton Sam , Luo Wei , Feng Weineng , Zhou Hongsheng , Liu Qifa , Chen Jiekai , Lai Liangxue , Chen Xinwen , Pei Duanqing , Graf Thomas , Liu Xingguo , Li Yangqiu , Liu Pentao , Zhang Zhenfeng , Li Peng
Published: March 2022

Background

Adoptive cell therapy (ACT) is a particularly promising area of cancer immunotherapy, engineered T and NK cells that express chimeric antigen receptors (CAR) are being explored for treating hematopoietic malignancies but exhibit limited clinical benefits for solid tumour patients, successful cellular immunotherapy of solid tumors demands new strategies.

Methods

Inactivation of BCL11B were performed by CRISPR/Cas9 in human T cells. Immunophenotypic and transcriptional profiles of sgBCL11B T cells were characterized by cytometer and transcriptomics, respectively. sgBCL11B T cells are further engineered with chimeric antigen receptor. Anti-tumor activity of ITNK or CAR-ITNK cells were evaluated in preclinical and clinical studies.

Results

We report that inactivation of BCL11B in human CD8+ and CD4+ T cells induced their reprogramming into induced T-to-natural killer cells (ITNKs). ITNKs contained a diverse TCR repertoire; downregulated T cell-associated genes such as TCF7 and LEF1; and expressed high levels of NK cell lineage-associated genes. ITNKs and chimeric antigen receptor (CAR)-transduced ITNKs selectively lysed a variety of cancer cells in culture and suppressed the growth of solid tumors in xenograft models. In a preliminary clinical study, autologous administration of ITNKs in patients with advanced solid tumors was well tolerated, and tumor stabilization was seen in six out nine patients, with one partial remission.

Conclusions

The novel ITNKs thus may be a promising novel cell source for cancer immunotherapy.

Trial registration

ClinicalTrials.gov, NCT03882840. Registered 20 March 2019-Retrospectively registered.
The National Health Cluster in Yemen: assessing the coordination of health response during humanitarian crises
Authors: Al-Awlaqi Sameh , Dureab Fekri , Tambor Marzena
Published: March 2022

Yemen has been facing political, economic and social challenges since 1990. The fragility of Yemen’s situation has led to a widespread conflict in 2015, resulting in the world’s largest humanitarian crisis. Amid the humanitarian catastrophe and the collapsing health system, a platform for coordinating humanitarian health response, called the National Health Cluster, has expanded its operations across the country. The study aims to evaluate the performance of the National Health Cluster in Yemen between 2015 and 2019. A qualitative research design was employed, and ten semi-structured interviews with key Health Cluster stakeholders were conducted. The study applied the Active Learning Network for Accountability and Performance in Humanitarian Action (ALNAP) guide to evaluating humanitarian action using the Development Assistance Committee (DAC) criteria. Six evaluation criteria were selected: relevance, effectiveness, efficiency, effects, connectedness and participation. Inputs from interviews were manually transcribed and then analysed using NVivo 12 software. The study results indicate that the Health Cluster in Yemen has contributed to saving lives and strengthening the local health capacities in diseases surveillance. In addition, its positive effect was evident in improving the humanitarian health response coordination.

Nevertheless, engaging health stakeholders, especially national organisations, was suboptimal. Exit strategies were lacking, while services to address mental health, non-communicable diseases, senior citizens and people with disabilities were not prioritised in the Health Cluster strategic plans and partners’ response. To ameliorate Health Cluster performance, revising its objectives and establishing a cluster-specific rapid response funding mechanism are pivotal. Furthermore, preparing the national health system for recovery and actively engaging all stakeholders in the Health Cluster’ response and strategic decisions would maximise its positive impact on Yemen’s health system and population.
The sequential mediation model of students’ willingness to continue online learning during the COVID-19 pandemic
Authors: Ngah Abdul Hafaz , Kamalrulzaman Nurul Izni , Mohamad Mohamad Firdaus Halimi , Rashid Rosyati Abdul , Harun Nor Omaima , Ariffin Nur Asma , Osman Noor Azuan Abu
Published: March 2022

This study explored the factors influencing students’ willingness to continue with the online learning system during the coronavirus disease 2019 (COVID-19) pandemic by adopting the stimulus–organism–response (SOR) theory. This study also incorporated e-learning readiness, performance, and satisfaction as mediators. The present study employed the purposive sampling method, whereby 2215 data of undergraduate students from a public university were gathered using an online survey and analysed using structural equation modelling (SEM) with Smart Partial Least Squares (SmartPLS). The results revealed that students’ e-learning readiness, performance, and satisfaction positively influenced their willingness to continue online learning. Besides, students’ e-learning readiness, performance, and satisfaction sequentially mediated the relationship between the online learning system quality and willingness to continue online learning. Significantly, this study provided new insights into the literature on students’ willingness to continue online learning by providing empirical evidence on the factors that support their willingness to continue online learning during the COVID-19 pandemic.
Computer vision syndrome and predictors among computer users in Ethiopia: a systematic review and meta-analysis
Authors: Adane Fentahun , Alamneh Yoseph Merkeb , Desta Melaku
Published: March 2022

Background

A computer is one of the most widely used office tools. The leading occupational health problem of the twenty-first century is computer vision syndrome (CVS). Research findings across Ethiopia on the magnitude and predictors of CVS among computer users are highly variable and inconsistent. Therefore, this study aimed to estimate the overall prevalence of CVS and its predictors among computer users in Ethiopia.

Methods

We searched articles in all databases and other sources. Cochrane Q test statistics and I2 tests were used. A random-effect meta-analysis model was used. In addition, the association between risk factors and CVS among computer users was examined.

Results

Eight eligible studies were included. The pooled prevalence of CVS among computer users in Ethiopia was 73.21% (95% CI 70.32–76.11). Sub-group analysis by profession has shown that the highest prevalence of CVS was observed in bank employees [73.76% (95% CI 70.40–77.13)]. The most common reported symptoms of CVS were blurred vision (34.26%; 95% CI 22.08, 46.43). The previous history of eye disease (95% CI 2.30, 5.47), inappropriate sitting position (95% CI 1.76, 3.22), the frequent use of a computer (95% CI 2.04, 3.60), and using eyeglass/spectacles (95% CI 1.10, 3.91) were significantly associated with CVS among computer users in Ethiopia.

Conclusions

According to this study, computer vision syndrome was high among computer users in Ethiopia. Computer vision syndrome (CVS) was significantly associated with a previous history of eye disease, inappropriate sitting position, frequent use of a computer, and the use of spectacles. Based on the findings, it is suggested that efforts be made to optimize computer exposure time. It is also worth noting that employees should be properly seated when using a computer. Furthermore, people with vision problems should be extra cautious when using a computer. Finally, community awareness of the safety precautions that can be taken to reduce CVS is critical.
High-speed Si-Ge avalanche photodiodes
Authors: Wang Binhao , Mu Jifang
Published: March 2022

High-speed optical interconnects of data centers and high performance computers (HPC) have become the rapid development direction in the field of optical communication owing to the explosive growth of market demand. Currently, optical interconnect systems are moving towards higher capacity and integration. High-sensitivity receivers with avalanche photodiodes (APDs) are paid more attention due to the capability to enhance gain bandwidth. The impact ionization coefficient ratio is one crucial parameter for avalanche photodiode optimization, which significantly affects the excess noise and the gain bandwidth product (GBP). The development of silicon-germanium (Si-Ge) APDs are promising thanks to the low impact ionization coefficient ratio of silicon, the simple structure, and the CMOS compatible process. Separate absorption charge multiplication (SACM) structures are typically adopted in Si-Ge APDs to achieve high bandwidth and low noise. This paper reviews design and optimization in high-speed Si-Ge APDs, including advanced APD structures, APD modeling and APD receivers.
Pilot Study of a Wearable Activity Monitor During Head and Neck Radiotherapy to Predict Clinical Outcomes
Authors: Sher David J. , Radpour Sepeadeh , Shah Jennifer L. , Pham Nhat-Long , Jiang Steve , Vo Dat , Sumer Baran D. , Day Andrew T.
Published: March 2022

PURPOSE

Given the established associations between performance status and survival in a variety of cancers, there is significant interest in using a biometric wearable device (WD) to predict outcomes in the oncology population. In this pilot study, we investigated the ability of a WD to predict meaningful clinical end points in patients undergoing head and neck radiotherapy.

METHODS

Patients receiving head and neck definitive chemoradiotherapy or postoperative radiotherapy/chemoradiotherapy were enrolled in this pilot study, designed to show 90% compliance with using the device. Individuals were asked to wear the WD for 23 hours a day, and hospital admissions, pain medication usage, and FACT-G quality-of-life (QoL) score were prospectively recorded.

RESULTS

Fifty-one patients were enrolled and started using the WD, but eight patients stopped wearing it, resulting in a compliance probability of only 84%. There were 15 hospital admissions, 13 of which were planned for feeding tube placement. There was no step count threshold that predicted the need for admission or more pain medications. However, among the 25 patients with a significant reduction in FACT-G score, the average reductions in daily steps during the week and weekend before the decline were 988 ( P = .005) and 1,311 ( P = .018), respectively, and the odds of a QoL reduction were more than 4-fold higher among patients experiencing a week-to-week reduction of at least 1,000 daily steps. There was no association between heart rate and any end point.

CONCLUSION

Although not meeting the compliance goal, the majority of patients did use the WD. The WD signal could not identify patients requiring hospitalization or significantly more pain medication, but the finding of reduced step counts before a significant reduction in QoL is provocative.
Biosimilar Versus Originator Pegfilgrastim for Preventing Chemotherapy-Induced Neutropenia: A Phase III Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study
Authors: Kowalyszyn Ruben D. , Fein Luis E. , Richardet Martin E. , Varela Mirta S. , Ortiz Eduardo , Micheri Cristian , Zarba Juan J. , Kahl Susana , Klimovsky Ezequiel , Federico Andrea A. , Cassini Jorge H. , Cortese Gustavo , Lago Nestor
Published: March 2022

PURPOSE

This study evaluated the efficacy, safety, and immunogenicity of biosimilar pegfilgrastim (PegFilBS) and originator pegfilgrastim (PegFilOR) in patients with stage 2-4 breast cancer.

METHODS

This phase III randomized, multicenter, evaluator-blinded, noninferiority study recruited women with stage 2-4 breast cancer in Argentina who were scheduled to receive chemotherapy. Stratification was based on the breast cancer stage. The primary end point was the duration of severe neutropenia (DSN, noninferiority margin: 1 day) in the first chemotherapy cycle. Secondary end points assessed were incidence of severe neutropenia, grade 3 neutropenia, febrile neutropenia, infections, postchemotherapy hospitalization and duration, and the incidence of adverse drug reactions (ADRs).

RESULTS

A total of 120 patients were randomly assigned to receive PegFilBS (58 patients) or PegFilOR (62 patients). Severe neutropenia occurred in 52 of 283 cycles (18.4%) for 27 patients who received PegFilBS and in 48 of 297 cycles (16.2%) for 20 patients who received PegFilOR ( P = .48). During the first cycle, severe neutropenia occurred in 16 patients who received PegFilBS (DSN: 0.78 ± 1.53 days) and in 11 patients who received PegFilOR (DSN: 0.53 ± 1.25 days; 95% CI, –0.26 to 0.76 days). In the intention-to-treat analysis, the mean DSN values were 0.90 ± 1.79 days for the PegFilBS group and 0.50 ± 1.21 for the PegFilOR group (95% CI, –0.15 to 0.95 days). No significant differences were observed for the secondary efficacy end points. Three patients experienced seven ADRs in the PegFilBS group while 10 patients experienced 31 ADRs in the PegFilOR group. The most common ADR was myalgia.

CONCLUSION

Relative to PegFilOR, PegFilBS provided noninferior efficacy outcomes in Argentinian women with stage 2-4 breast cancer who were treated using myelosuppressive chemotherapy.
Outcomes of Cervical Cancer in HIV-Positive Women Treated With Radiotherapy at a Tertiary Care Center in India
Authors: Gurram Lavanya , Mohanty Samarpita , Chopra Supriya , Grover Surbhi , Engineer Reena , Gupta Sudeep , Ghosh Jaya , Gulia Seema , Sawant Sheela , Daddi Anuprita , Deodhar Kedar , Menon Santosh , Rekhi Bharat , Shylasree T.S. , Maheshwari Amita , Mahantshetty Umesh
Published: March 2022

PURPOSE

There are limited data on management of cervical cancer in women living with HIV in the modern antiretroviral therapy era. The study aimed to evaluate outcomes and toxicities of these patients treated with radiotherapy.

MATERIALS AND METHODS

A retrospective analysis of HIV-positive cervical cancer patients treated with radiotherapy between 2011 and 2018 was conducted at a tertiary care center in India.

RESULTS

Eighty-two HIV-positive cervical cancer patients treated with radiotherapy were identified. Their median age was 45 years. Seventy-four (90%) patients received radiotherapy with curative-intent and eight patients received palliative radiotherapy. Median CD4 count at the start of treatment was 342 cells/mm3 (interquartile range: 241-531). Among patients planned for definitive radiotherapy, concurrent cisplatin was planned in 52 (70%) patients with a median of four chemotherapy cycles, and 81% (n = 60) patients received brachytherapy. Among patients who received brachytherapy, the median prescription dose was 80 Gy. Seventy-seven patients completed their prescribed treatment. At a median follow-up of 37 months, 3-year disease-free survival of patients planned with curative-intent was 54%. On multivariate analysis, treatment completion was associated with favorable disease-free survival. Grade III/IV acute gastrointestinal toxicity was seen in five (6.8%) patients, whereas 30% patients had grade III/IV acute hematologic toxicity. All these patients completed their planned radiotherapy with good supportive care.

CONCLUSION

Standard treatment of chemoradiation should be planned in women living with HIV with well-managed HIV presenting with locally advanced cervical cancer. Our study highlights the need for optimal management of these patients by a multidisciplinary team with intensive supportive care to ensure completion of planned treatment to achieve better outcomes.
Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma
Authors: Wang Ying , Cao Jiang , Gu Weiying , Shi Ming , Lan Jianping , Yan Zhiling , Jin Lai , Xia Jieyun , Ma Sha , Liu Yang , Li Hujun , Pan Bin , Chen Wei , Fei Xiaoming , Wang Chunling , Xie Xiaobao , Yu Liang , Wang Gang , Li Huizhong , Jing Guangjun , Cheng Hai , Zhu Feng , Sun Haiying , Sang Wei , Li Depeng , Li Zhenyu , Zheng Junnian , Xu Kailin
Published: March 2022

PURPOSE

A combination of anti–B-cell maturation antigen (BCMA) and anti-CD19 chimeric antigen receptor (CAR) T cells induced high response rates in patients with relapsed or refractory (R/R) multiple myeloma (MM), but long-term outcomes have not been assessed yet.

PATIENTS AND METHODS

In this single-arm, phase II trial, patients with R/R MM received a combination of anti-BCMA CAR T cells and anti-CD19 CAR T cells at a dose of 1 × 106 cells/kg, after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine. The overall response, long-term outcomes, and safety were assessed, as were their associations with clinical and disease characteristics.

RESULTS

Of 69 enrolled patients, 62 received the combined infusion of anti-BCMA and anti-CD19 CAR T cells with a median follow-up of 21.3 months. The overall response rate was 92% (57/62), and complete response or better was observed in 37 patients (60%). Minimal residual disease–negativity was confirmed in 77% (43/56) of the patients with available minimal residual disease detection. The estimated median duration of response was 20.3 months (95% CI, 9.1 to 31.5). The median progression-free survival was 18.3 months (95% CI, 9.9 to 26.7), and the median overall survival was not reached. Patients with extramedullary disease had significantly inferior survival. Fifty-nine patients (95%) had cytokine release syndrome, with 10% grade 3 or higher. Neurotoxic events occurred in seven patients (11%), including 3% grade 3 or higher. Late adverse effects were rare, except for B-cell aplasia, hypogammaglobulinemia, and infections.

CONCLUSION

The combination of anti-BCMA and anti-CD19 CAR T cells induced durable response in patients with R/R MM, with a median progression-free survival of 18.3 months and a manageable long-term safety profile.