bluuebunny/crossref_metadata_2025 huggingface dataset:
The leptin receptor has no role in delta-cell control of beta-cell function in the mouse
Authors: Zhang Jia , Katada Kay , Mosleh Elham , Yuhas Andrew , Peng Guihong , Golson Maria L.
Published: October 2023

Introduction

Leptin inhibits insulin secretion from isolated islets from multiple species, but the cell type that mediates this process remains elusive. Several mouse models have been used to explore this question. Ablation of the leptin receptor (Lepr) throughout the pancreatic epithelium results in altered glucose homeostasis and ex vivo insulin secretion and Ca2+ dynamics. However, Lepr removal from neither alpha nor beta cells mimics this result. Moreover, scRNAseq data has revealed an enrichment of LEPR in human islet delta cells.

Methods

We confirmed LEPR upregulation in human delta cells by performing RNAseq on fixed, sorted beta and delta cells. We then used a mouse model to test whether delta cells mediate the diminished glucose-stimulated insulin secretion in response to leptin.

Results

Ablation of Lepr within mouse delta cells did not change glucose homeostasis or insulin secretion, whether mice were fed a chow or high-fat diet. We further show, using a publicly available scRNAseq dataset, that islet cells expressing Lepr lie within endothelial cell clusters.

Conclusions

In mice, leptin does not influence beta-cell function through delta cells.
Insulin and aging – a disappointing relationship
Authors: Kolb Hubert , Kempf Kerstin , Martin Stephan
Published: October 2023

Experimental studies in animal models of aging such as nematodes, fruit flies or mice have observed that decreased levels of insulin or insulin signaling promotes longevity. In humans, hyperinsulinemia and concomitant insulin resistance are associated with an elevated risk of age-related diseases suggestive of a shortened healthspan. Age-related disorders include neurodegenerative diseases, hypertension, cardiovascular disease, and type 2 diabetes. High ambient insulin concentrations promote increased lipogenesis and fat storage, heightened protein synthesis and accumulation of non-functional polypeptides due to limited turnover capacity. Moreover, there is impaired autophagy activity, and less endothelial NO synthase activity. These changes are associated with mitochondrial dysfunction and oxidative stress. The cellular stress induced by anabolic activity of insulin initiates an adaptive response aiming at maintaining homeostasis, characterized by activation of the transcription factor Nrf2, of AMP activated kinase, and an unfolded protein response. This protective response is more potent in the long-lived human species than in short-lived models of aging research resulting in a stronger pro-aging impact of insulin in nematodes and fruit flies. In humans, resistance to insulin-induced cell stress decreases with age, because of an increase of insulin and insulin resistance levels but less Nrf2 activation. These detrimental changes might be contained by adopting a lifestyle that promotes low insulin/insulin resistance levels and enhances an adaptive response to cellular stress, as observed with dietary restriction or exercise.
New perspectives on the evolutionary history of xiphosuran development through comparison with other fossil euchelicerates
Authors: Lustri Lorenzo , Antcliffe Jonathan B. , Saleh Farid , Haug Carolin , Laibl Lukáš , Garwood Russell J. , Haug Joachim T. , Daley Allison C.
Published: October 2023

Introduction

Euchelicerata is a diverse group encompassing Xiphosura, Chasmataspidida, Eurypterida, and Arachnida. Xiphosura represents an extant group with a rich fossil record dating back to the Ordovician period. Xiphosurans are often referred to as “living fossils” due to their seemingly unchanged morphology over millions of years. Numerous studies have contributed to the understanding of xiphosuran development, revealing changes in the timing and rate of their growth. These changes have been mainly associated with the freshwater invasion of early xiphosuran forms. However, limited research has been conducted to compare the developmental patterns of xiphosurans with other euchelicerates inhabiting aquatic environments.

Methods

This study compares the developmental patterns of xiphosurans with that of the fossil clades of eurypterids and chasmataspidids. By incorporating environmental and phylogenetic information within ancestral state reconstruction analyses, and then testing different evolutionary scenarios, the influence of the environment on the evolution of developmental patterns of euchelicerates is examined.

Results

The results confirm that the developmental changes in Xiphosura throughout their evolutionary history are correlated with the exploitation of different environments. However, the inclusion of eurypterids and chasmataspidids indicates that the entirety of changes seen for Xiphosura represent only a small portion of the total variability recovered for euchelicerates.

Discussion

Our results emphasize the importance of considering phylogenetic relationships and outgroup comparisons to understand the evolutionary dynamics of Xiphosura.
Sensehacking passenger wellbeing while in the air
Authors: Spence Charles
Published: October 2023

Air travel has undoubtedly become a more stressful activity for many passengers in recent years, in part as a result of the global Covid pandemic. Consequently, there has been a growing focus on how to optimize the psychological wellbeing of passengers while in the air. This narrative historical review considers how the passenger experience can potentially be hacked through the more intelligent stimulation of the travellers’ senses. In particular, the focus is on promoting passenger comfort, enhancing the provision of healthy food and beverage options/experiences, facilitating relaxation and sleep and, when appropriate, boosting passengers’ arousal/alertness as well (e.g., prior to arrival). A number of concrete suggestions concerning how to sensehack passenger wellbeing at the various stages while in the air are made.
Maternal satisfaction with intrapartum care and associated factors among mothers who gave birth in public hospitals of the South West Shewa Zone, Ethiopia, 2022
Authors: Tolesa Fikadu , Alemu Adugna , Beya Moges , Feyisa Mulugeta , Gezahagn Andualem , Negash Abdi , Shigign Erean , Getaye Asfaw , Negash Abraham , Merga Bacha
Published: October 2023

Background

Maternal satisfaction with intrapartum care is a multidimensional assumption of satisfaction with self and with the physical environment of the delivery ward and quality of care. Maternal satisfaction with intrapartum care affects the selection of birthplace and helps to identify gaps between actual and intended healthcare outcomes. This study aims to assess factors that affect maternal satisfaction with intrapartum care.

Objectives

To assess maternal satisfaction with intrapartum care and associated factors among mothers who gave birth in public hospitals in the South-west Shewa Zone, Ethiopia, 2022.

Methods

A cross-sectional study approach among 420 mothers was conducted between April 14 and June 14, 2022. Systematic random sampling was used to select mothers for face-to-face interviews every two intervals. Bivariate and multivariable logistic regression analyses were carried out. P-values of <0.25 in association with study variables were transferred to multivariable logistic regression models. An adjusted odds ratio with a 95% confidence interval was computed, and p-values of <0.05 were considered statistically significant in the multivariable model. The results of this study are presented using text, tables, and charts.

Results

Data were collected from 420 participants, and 413 mothers completed the interview, giving a response rate of 98.33%. The overall maternal satisfaction with intrapartum care was 245 (59.32%) [95% CI: 55–64]. Mothers who were considered normal during labor and delivery (AOR = 2.57 (95% CI: 1.30–5.07), had a labor duration of 12 h or less (AOR = 1.59 (95% CI: 1.03–2.44), and experienced a waiting time of <15 min (AOR = 2.06 (95% CI: 1.21–3.52) were significantly associated with maternal satisfaction with intrapartum care.

Conclusion and Recommendations

More than half of mothers were satisfied with the overall intrapartum care they received. Health facility managers and healthcare providers work together to improve maternal satisfaction with intrapartum care.
Single-cell profiling reveals immune disturbances landscape and HLA-F-mediated immune tolerance at the maternal-fetal interface in preeclampsia
Authors: Luo Fangyuan , Liu Fulin , Guo Yingzhe , Xu Wenming , Li Yilin , Yi Jun , Fournier Thierry , Degrelle Séverine , Zitouni Hedia , Hernandez Isabelle , Liu Xinghui , Huang Yu , Yue Jun
Published: October 2023

Background

Preeclampsia is a pregnancy-specific disorder that always causes maternal and fetal serious adverse outcome. Disturbances in maternal immune tolerance to embryo at the maternal-fetal interface (MFI) may be associated with preeclampsia onset. Recent studies have revealed the reduced expression pattern of HLA-F at the MFI in preeclampsia, while the mechanism of it mediating maternal fetal immune tolerance has not been revealed.

Methods

Single-cell RNA sequencing on placental decidua was performed to reveal the immune disturbances landscape at the MFI in preeclampsia. Human Jar cells and NK-92MI cells were employed to study the role of HLA-F in trophoblasts and lymphocyte.

Results

A total of 101,250 cells were classified into 22 cell clusters. Disease-related IGFBP1+SPP1+ extracellular villus trophoblast (EVT) was identified in the preeclamptic placental decidua, accompanied by newly discovered immune cellular dysfunction such as reduced ribosomal functions of NK populations and abnormal expression of antigen-presenting molecules in most cell clusters. Certain genes that are characteristic of the intermediate stage of myeloid or EVT cell differentiation were found to have unexplored but important functions in the pathogenesis of preeclampsia; specifically, we detected enhanced cell cross-talk between IGFBP1+SPP1+ EVT2 or SPP1+M1 cells and their receptor cell populations at the MFI of PE patients compared to controls. With respect to HLA-F, mIF staining confirmed its reduced expression in PE samples compared to controls. Over-expression of HLA-F in Jar cells promoted cell proliferation, invasion, and migration while under-expression had the opposite effect. In NK-92MI cells, over-expression of HLA-F increased the secretion of immunoregulation cytokines such as CSF1 and CCL22, and promoted adaptive NKG2C+NK cell transformation.

Conclusions

We revealed the immune disturbance landscape at the MFI in preeclampsia. Our findings regarding cellular heterogeneity and immune cellular dysfunction, as revealed by scRNA-seq, and the function of HLA-F in cells provide new perspectives for further investigation of their roles in the pathogenesis of preeclampsia, and then provide potential new therapeutic target.
Unraveling molecular networks in thymic epithelial tumors: deciphering the unique signatures
Authors: Zhang Xiao , Zhang Pengpeng , Cong Ansheng , Feng Yanlong , Chi Hao , Xia Zhijia , Tang Hailin
Published: October 2023

Thymic epithelial tumors (TETs) are a rare and diverse group of neoplasms characterized by distinct molecular signatures. This review delves into the complex molecular networks of TETs, highlighting key aspects such as chromosomal abnormalities, molecular subtypes, aberrant gene mutations and expressions, structural gene rearrangements, and epigenetic changes. Additionally, the influence of the dynamic tumor microenvironment on TET behavior and therapeutic responses is examined. A thorough understanding of these facets elucidates TET pathogenesis, offering avenues for enhancing diagnostic accuracy, refining prognostic assessments, and tailoring targeted therapeutic strategies. Our review underscores the importance of deciphering TETs’ unique molecular signatures to advance personalized treatment paradigms and improve patient outcomes. We also discuss future research directions and anticipated challenges in this intriguing field.
Analysis of gut bacteriome of in utero arsenic-exposed mice using 16S rRNA-based metagenomic approach
Authors: Shukla Shagun , Srivastava Ankita , Verma Digvijay , Gangopadhyay Siddhartha , Chauhan Anchal , Srivastava Vikas , Budhwar Savita , Tyagi Dushyant , Sharma Deepak Chand
Published: October 2023

Introduction

Approximately 200 million people worldwide are affected by arsenic toxicity emanating from the consumption of drinking water containing inorganic arsenic above the prescribed maximum contaminant level. The current investigation deals with the role of prenatal arsenic exposure in modulating the gut microbial community and functional pathways of the host.

Method

16S rRNA-based next-generation sequencing was carried out to understand the effects of in utero 0.04 mg/kg (LD) and 0.4 mg/kg (HD) of arsenic exposure. This was carried out from gestational day 15 (GD-15) until the birth of pups to understand the alterations in bacterial diversity.

Results

The study focused on gestational exposure to arsenic and the altered gut microbial community at phyla and genus levels, along with diversity indices. A significant decrease in firmicutes was observed in the gut microbiome of mice treated with arsenic. Functional analysis revealed that a shift in genes involved in crucial pathways such as insulin signaling and non-alcoholic fatty liver disease pathways may lead to metabolic diseases in the host.

Discussion

The present investigation may hypothesize that in utero arsenic exposure can perturb the gut bacterial composition significantly as well as the functional pathways of the gestationally treated pups. This research paves the way to further investigate the probable mechanistic insights in the field of maternal exposure environments, which may play a key role in epigenetic modulations in developing various disease endpoints in the progeny.
Serpentinization as the source of energy, electrons, organics, catalysts, nutrients and pH gradients for the origin of LUCA and life
Authors: Schwander Loraine , Brabender Max , Mrnjavac Natalia , Wimmer Jessica L. E. , Preiner Martina , Martin William F.
Published: October 2023

Serpentinization in hydrothermal vents is central to some autotrophic theories for the origin of life because it generates compartments, reductants, catalysts and gradients. During the process of serpentinization, water circulates through hydrothermal systems in the crust where it oxidizes Fe (II) in ultramafic minerals to generate Fe (III) minerals and H2. Molecular hydrogen can, in turn, serve as a freely diffusible source of electrons for the reduction of CO2 to organic compounds, provided that suitable catalysts are present. Using catalysts that are naturally synthesized in hydrothermal vents during serpentinization H2 reduces CO2 to formate, acetate, pyruvate, and methane. These compounds represent the backbone of microbial carbon and energy metabolism in acetogens and methanogens, strictly anaerobic chemolithoautotrophs that use the acetyl-CoA pathway of CO2 fixation and that inhabit serpentinizing environments today. Serpentinization generates reduced carbon, nitrogen and — as newer findings suggest — reduced phosphorous compounds that were likely conducive to the origins process. In addition, it gives rise to inorganic microcompartments and proton gradients of the right polarity and of sufficient magnitude to support chemiosmotic ATP synthesis by the rotor-stator ATP synthase. This would help to explain why the principle of chemiosmotic energy harnessing is more conserved (older) than the machinery to generate ion gradients via pumping coupled to exergonic chemical reactions, which in the case of acetogens and methanogens involve H2-dependent CO2 reduction. Serpentinizing systems exist in terrestrial and deep ocean environments. On the early Earth they were probably more abundant than today. There is evidence that serpentinization once occurred on Mars and is likely still occurring on Saturn’s icy moon Enceladus, providing a perspective on serpentinization as a source of reductants, catalysts and chemical disequilibrium for life on other worlds.
Lactobacillus (Limosilactobacillus) reuteri: a probiotic candidate to reduce neonatal diarrhea in calves
Authors: Schwaiger Karin , Storch Julia , Bauer Christoph , Bauer Johann
Published: October 2023

Background

Diarrhea in newborn calves is considered life-threatening and results in large economic losses in dairy farms. Lactobacilli generally play an important role in intestinal health, and Lactobacillus (Limosilactobacillus; L.) reuteri is the dominant Lactobacillus species in the feces of healthy calves during the first week of life. In calves with diarrhea on day 2 postpartum, lactobacilli are significantly reduced even up to 24 h before the onset of clinical signs. Since the probability of occurrence of diarrheal disease decreases as the L. reuteri count in the feces increases, oral administration of this species might have a protective effect against diarrhea.

Objective

These studies were designed to demonstrate whether oral administration of preselected L. reuteri isolates can reduce the incidence of diarrhea in newborn calves on dairy farms.

Microorganisms

46 L. reuteri isolates from 2-day-old healthy calves were available from a previous study.

Animals

170 newborn calves of Simmental breed of 10 dairy farms in Bavaria (Germany), were included in the study; of 166 animals the data could be evaluated.

Methods

Microbiological (antibiotic sensitivity test, acid and bile salt stability test, antimicrobial activity of the supernatants), molecular biological (PCR, RAPD-PCR) and toxicological methods (MTT test) were used to select and to characterize suitable L. reuteri isolates. The administration of a suspension of two selected L. reuteri isolates (6–8 × 108 colony forming units per day) to calves was performed from day 2 to day 5 after birth in a double-blinded placebo-controlled study. Clinical monitoring of the calves continued until the 14th day of life.

Results

Out of 46 L. reuteri isolates, only 2 met the set criteria and were used in the feeding trial. In the placebo group, 44 of 83 calves developed diarrhea within the first 2 weeks of life, whereas in the L. reuteri group this was only the case in 31 of 83 animals (p < 0.05).

Conclusion

L. reuteri appears to be of particular importance for the intestinal health of newborn calves. The diarrhea protective effect could be even more pronounced if an improved administration regimen is developed in terms of start, frequency, and duration.
Mechanism of action of sprG1-encoded type I toxins in Staphylococcus aureus: from membrane alterations to mesosome-like structures formation and bacterial lysis
Authors: Fermon Laurence , Burel Agnès , Ostyn Emeline , Dréano Stéphane , Bondon Arnaud , Chevance Soizic , Pinel-Marie Marie-Laure
Published: October 2023

sprG1/SprF1 is a type I toxin-antitoxin system located on Staphylococcus aureus prophage. It has previously been shown that the two toxins, SprG131 and SprG144, encoded by the sprG1 gene, are two membrane-associated peptides structured in a single α-helix. Overexpression of these two peptides leads to growth inhibition and even S. aureus death. In this study, we investigated the involvement of each peptide in this toxicity, the sequence requirements necessary for SprG131 toxicity, and the mechanism of action of these two peptides. Our findings show that both peptides, when expressed individually, are able to stop growth, with higher toxicity observed for SprG131. The combination of a hydrophobic domain and a charged domain located only at the C-terminus is necessary for this toxicity, likely to retain the orientation of the transmembrane domain. A net cationic charge for SprG131 is not essential to induce a growth defect in S. aureus. Furthermore, we established a chronology of toxic events following overexpression to gain insights into the mode of action of SprG144 and SprG131. We demonstrated that mesosome-like structures are already formed when membrane is depolarized, about 20 min after peptides induction. This membrane depolarization occurs concomitantly with a depletion of intracellular ATP, leading to S. aureus growth arrest. Moreover, we hypothesized that SprG144 and SprG131 do not form large pores in the S. aureus membrane, as ATP is not excreted into the extracellular medium, and membrane permeabilization is delayed relative to membrane depolarization. The next challenge is to identify the conditions under which SprG144 and SprG131 are naturally expressed, and to uncover their potential roles during staphylococcal growth, colonization, and infection.
AI/ML combined with next-generation sequencing of VHH immune repertoires enables the rapid identification of de novo humanized and sequence-optimized single domain antibodies: a prospective case study
Authors: Arras Paul , Yoo Han Byul , Pekar Lukas , Clarke Thomas , Friedrich Lukas , Schröter Christian , Schanz Jennifer , Tonillo Jason , Siegmund Vanessa , Doerner Achim , Krah Simon , Guarnera Enrico , Zielonka Stefan , Evers Andreas
Published: October 2023

Introduction: In this study, we demonstrate the feasibility of yeast surface display (YSD) and nextgeneration sequencing (NGS) in combination with artificial intelligence and machine learning methods (AI/ML) for the identification of de novo humanized single domain antibodies (sdAbs) with favorable early developability profiles.

Methods: The display library was derived from a novel approach, in which VHH-based CDR3 regions obtained from a llama (Lama glama), immunized against NKp46, were grafted onto a humanized VHH backbone library that was diversified in CDR1 and CDR2. Following NGS analysis of sequence pools from two rounds of fluorescence-activated cell sorting we focused on four sequence clusters based on NGS frequency and enrichment analysis as well as in silico developability assessment. For each cluster, long short-term memory (LSTM) based deep generative models were trained and used for the in silico sampling of new sequences. Sequences were subjected to sequence- and structure-based in silico developability assessment to select a set of less than 10 sequences per cluster for production.

Results: As demonstrated by binding kinetics and early developability assessment, this procedure represents a general strategy for the rapid and efficient design of potent and automatically humanized sdAb hits from screening selections with favorable early developability profiles.
Dietary intake of total vegetable, fruit, cereal, soluble and insoluble fiber and risk of all-cause, cardiovascular, and cancer mortality: systematic review and dose–response meta-analysis of prospective cohort studies
Authors: Yao Feifei , Ma Jianping , Cui Yong , Huang Cuihong , Lu Ruiqi , Hu Fulan , Zhu Xiaoming , Qin Pei
Published: October 2023

Objectives

To conduct a systematic review and meta-analysis of prospective cohort studies to investigate the association between total, vegetable, fruit, cereal, soluble and insoluble fiber intake and risk of all causes, cardiovascular disease (CVD), and cancer mortality and quantitatively assess the dose–response relation.

Methods

Eligible studies were identified by searching PubMed, Embase and Web of science before August 2023. Random effects models were used to calculate summary relative risk (RR) and 95% confidence intervals (CI) and restricted cubic splines to model the linear/non-linear association.

Results

The summary RR for all-cause, CVD and cancer mortality of dietary fiber was 0.90 (95% CI: 0.86,0.93), 0.87 (0.84,0.91), 0.91 (0.88,0.93), respectively. Significant association was observed for all-cause and CVD mortality with fruit, vegetable cereal and soluble fiber intake and cancer mortality with cereal fiber intake. No significant association was found for insoluble fiber, vegetable or fruit fiber intake and cancer mortality. Dose-response analysis showed a significant non-linear relation of dietary fiber intake with all-cause mortality, and linear relation for others.

Conclusions

Higher dietary fiber including different type and food sources of fiber intake were associated with lower risk of mortality. Our findings provide more comprehensive evidence on dietary fiber intake with mortality.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier: CRD42022338837.
Neoadjuvant chemotherapy for breast cancer: an evaluation of its efficacy and research progress
Authors: Chen Yushi , Qi Yu , Wang Kuansong
Published: October 2023

Neoadjuvant chemotherapy (NAC) for breast cancer is widely used in the clinical setting to improve the chance of surgery, breast conservation and quality of life for patients with advanced breast cancer. A more accurate efficacy evaluation system is important for the decision of surgery timing and chemotherapy regimen implementation. However, current methods, encompassing imaging techniques such as ultrasound and MRI, along with non-imaging approaches like pathological evaluations, often fall short in accurately depicting the therapeutic effects of NAC. Imaging techniques are subjective and only reflect macroscopic morphological changes, while pathological evaluation is the gold standard for efficacy assessment but has the disadvantage of delayed results. In an effort to identify assessment methods that align more closely with real-world clinical demands, this paper provides an in-depth exploration of the principles and clinical applications of various assessment approaches in the neoadjuvant chemotherapy process.
Does perioperative allogeneic blood transfusion worsen the prognosis of patients with hepatocellular carcinoma? A meta-analysis of propensity score-matched studies
Authors: Hu Lingbo , Li Zhenyu , Qiao Yingli , Wang Aidong
Published: October 2023

Background

Allogeneic blood transfusion is required in a part of liver resection. The effect of allogeneic blood transfusion on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. To investigate whether perioperative allogeneic blood transfusion (PBT) affects the long-term prognosis of patients with HCC, we conducted a meta-analysis that included only propensity score-matched (PSM) studies.

Methods

The Cochrane Library, Embase, PubMed, and Web of Science databases were systematically searched to identify PSM studies that compared the long-term outcomes of allogeneic blood transfusion in resected HCC patients. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated.

Results

This meta-analysis included 9 PSM studies with 12 datasets involving 2476 patients. Lower OS and RFS in HCC patients receiving allogeneic blood transfusion were observed than those in patients not receiving blood transfusion (OS: hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.10–1.64; p < 0.01; RFS: HR, 1.29; 95% CI, 1.07–1.56; p < 0.01). Subgroup analysis revealed that among patients with BCLC A HCC, those receiving allogeneic blood transfusion had lower OS and RFS (OS: HR, 2.27; 95% CI, 1.61–3.21; RFS: HR, 2.11; 95% CI, 1.30–3.41). OS and RFS were similar in both groups of patients with BCLC B and C HCC.

Conclusion

The receipt of perioperative allogeneic blood transfusion is associated with a decrease in OS and RFS. These results seem to be reliable for patients in BCLC stage A. But more high-quality research is needed to confirm this conclusion.
Real-world outcomes of diffuse large B-cell lymphoma in the biosimilar era
Authors: Nair Reena , Bhat Gull Mohammad , Agrawal Narendra , Sengar Manju , Malhotra Pankaj , Nityanand Soniya , Lele Chitra , Reddy Pramod , Kankanwadi Suresh , Maharaj Narendra
Published: October 2023

Background

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and the most common type of non-Hodgkin lymphoma (NHL). The clinical use of rituximab has improved the treatment response and survival of patients with DLBCL. The introduction of rituximab biosimilar into healthcare system has helped in providing a cost-effective treatment to B-cell lymphoid malignancies as standard of care and has improved access to patients worldwide. The aim of this study was to observe the real-world effectiveness and safety of Reditux™ and Ristova®in DLBCL patients.

Methods

Observational study in adults with DLBCL receiving Reditux™ or Ristova®across 29 centers in India (2015–2022). Effectiveness and safety were assessed up to 2 years after first dose.

Results

Out of 1,365 patients considered for analysis, 1,250 (91.6%) were treated with Reditux™ and 115 (8.42%) with Ristova®. At 2 years, progression-free survival (PFS) 69% [hazard ratio (HR), 1.16; 95% CI, 0.80–1.67], overall survival (OS) 78.7% (HR, 1.20; 95% CI, 0.78–1.86), response rates, quality of life (QoL), and overall safety in both the cohorts were comparable. The best overall response rate (BORR) at 6 months was comparable with no statistically significant differences between the Reditux™ and the Ristova®cohorts (89.2% vs. 94.3%). In multivariate analysis, BCL-2 and VAS were significant prognostic factors for PFS.

Conclusion

Reditux™ and Ristova®were comparable in real-world setting.

Clinical Trial Registration

ISRCTN registry, identifier (ISRCTN13301166)
Predicting head and neck cancer treatment outcomes with pre-treatment quantitative ultrasound texture features and optimising machine learning classifiers with texture-of-texture features
Authors: Safakish Aryan , Sannachi Lakshmanan , DiCenzo Daniel , Kolios Christopher , Pejović-Milić Ana , Czarnota Gregory J.
Published: October 2023

Aim

Cancer treatments with radiation present a challenging physical toll for patients, which can be justified by the potential reduction in cancerous tissue with treatment. However, there remain patients for whom treatments do not yield desired outcomes. Radiomics involves using biomedical images to determine imaging features which, when used in tandem with retrospective treatment outcomes, can train machine learning (ML) classifiers to create predictive models. In this study we investigated whether pre-treatment imaging features from index lymph node (LN) quantitative ultrasound (QUS) scans parametric maps of head & neck (H&N) cancer patients can provide predictive information about treatment outcomes.

Methods

72 H&N cancer patients with bulky metastatic LN involvement were recruited for study. Involved bulky neck nodes were scanned with ultrasound prior to the start of treatment for each patient. QUS parametric maps and related radiomics texture-based features were determined and used to train two ML classifiers (support vector machines (SVM) and k-nearest neighbour (k-NN)) for predictive modeling using retrospectively labelled binary treatment outcomes, as determined clinically 3-months after completion of treatment. Additionally, novel higher-order texture-of-texture (TOT) features were incorporated and evaluated in regards to improved predictive model performance.

Results

It was found that a 7-feature multivariable model of QUS texture features using a support vector machine (SVM) classifier demonstrated 81% sensitivity, 76% specificity, 79% accuracy, 86% precision and an area under the curve (AUC) of 0.82 in separating responding from non-responding patients. All performance metrics improved after implementation of TOT features to 85% sensitivity, 80% specificity, 83% accuracy, 89% precision and AUC of 0.85. Similar trends were found with k-NN classifier.

Conclusion

Binary H&N cancer treatment outcomes can be predicted with QUS texture features acquired from index LNs. Prediction efficacy improved by implementing TOT features following methodology outlined in this work.
Microenvironmental immune cell alterations across the spectrum of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma
Authors: Panayi Christos , Akarca Ayse U. , Ramsay Alan D. , Shankar Ananth G. , Falini Brunangelo , Piris Miguel A. , Linch David , Marafioti Teresa
Published: October 2023

Background

The clinicopathological spectrum of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), also known as nodular lymphocyte predominant B-cell lymphoma, partially overlaps with T-cell/histiocyte-rich large B-cell lymphoma (THRLCBL). NLPHL histology may vary in architecture and B-cell/T-cell composition of the tumour microenvironment. However, the immune cell phenotypes accompanying different histological patterns remain poorly characterised.

Methods

We applied a multiplexed immunofluorescence workflow to identify differential expansion/depletion of multiple microenvironmental immune cell phenotypes between cases of NLPHL showing different histological patterns (as described by Fan et al, 2003) and cases of THRLBCL.

Results

FOXP3-expressing T-regulatory cells were conspicuously depleted across all NLPHL cases. As histology progressed to variant Fan patterns C and E of NLPHL and to THRLBCL, there were progressive expansions of cytotoxic granzyme-B-expressing natural killer and CD8-positive T-cells, PD1-expressing CD8-positive T-cells, and CD163-positive macrophages including a PDL1-expressing subset. These occurred in parallel to depletion of NKG2A-expressing natural killer and CD8-positive T-cells.

Discussion

These findings provide new insights on the immunoregulatory mechanisms involved in NLPHL and THLRBCL pathogenesis, and are supportive of an increasingly proposed biological continuum between these two lymphomas. Additionally, the findings may help establish new biomarkers of high-risk disease, which could support a novel therapeutic program of immune checkpoint interruption targeting the PD1:PDL1 and/or NKG2A:HLA-E axes in the management of high-risk NLPHL and THRLBCL.
Revealing the dynamic landscape of drug-drug interactions through network analysis
Authors: Jeong Eugene , Malin Bradley , Nelson Scott D. , Su Yu , Li Lang , Chen You
Published: October 2023

Introduction: The landscape of drug-drug interactions (DDIs) has evolved significantly over the past 60 years, necessitating a retrospective analysis to identify research trends and under-explored areas. While methodologies like bibliometric analysis provide valuable quantitative perspectives on DDI research, they have not successfully delineated the complex interrelations between drugs. Understanding these intricate relationships is essential for deciphering the evolving architecture and progressive transformation of DDI research structures over time. We utilize network analysis to unearth the multifaceted relationships between drugs, offering a richer, more nuanced comprehension of shifts in research focus within the DDI landscape.

Methods: This groundbreaking investigation employs natural language processing, techniques, specifically Named Entity Recognition (NER) via ScispaCy, and the information extraction model, SciFive, to extract pharmacokinetic (PK) and pharmacodynamic (PD) DDI evidence from PubMed articles spanning January 1962 to July 2023. It reveals key trends and patterns through an innovative network analysis approach. Static network analysis is deployed to discern structural patterns in DDI research, while evolving network analysis is employed to monitor changes in the DDI research trend structures over time.

Results: Our compelling results shed light on the scale-free characteristics of pharmacokinetic, pharmacodynamic, and their combined networks, exhibiting power law exponent values of 2.5, 2.82, and 2.46, respectively. In these networks, a select few drugs serve as central hubs, engaging in extensive interactions with a multitude of other drugs. Interestingly, the networks conform to a densification power law, illustrating that the number of DDIs grows exponentially as new drugs are added to the DDI network. Notably, we discovered that drugs connected in PK and PD networks predominantly belong to the same categories defined by the Anatomical Therapeutic Chemical (ATC) classification system, with fewer interactions observed between drugs from different categories.

Discussion: The finding suggests that PK and PD DDIs between drugs from different ATC categories have not been studied as extensively as those between drugs within the same categories. By unearthing these hidden patterns, our study paves the way for a deeper understanding of the DDI landscape, providing valuable information for future DDI research, clinical practice, and drug development focus areas.
Formulation of zinc foliar sprays for wheat grain biofortification: a review of current applications and future perspectives
Authors: Sánchez-Palacios José Tonatiuh , Henry David , Penrose Beth , Bell Richard
Published: October 2023

Agronomic biofortification of wheat grain with zinc can improve the condition of about one billion people suffering from zinc (Zn) deficiency. However, with the challenge of cultivating high-yielding wheat varieties in Zn-deficient soils and the global need to produce higher-quality food that nourishes the growing population, innovation in the strategies to deliver Zn directly to plants will come into play. Consequently, existing foliar formulations will need further refinement to maintain the high agronomic productivity required in competitive global grain markets while meeting the dietary Zn intake levels recommended for humans. A new generation of foliar fertilisers that increase the amount of Zn assimilated in wheat plants and the translocation efficiency of Zn from leaves to grains can be a promising solution. Research on the efficacy of adjuvants and emerging nano-transporters relative to conventional Zn forms applied as foliar fertilisers to wheat has expanded rapidly in recent years. This review scopes the range of evidence available in the literature regarding the biofortification of bread wheat (Triticum aestivum L.) resulting from foliar applications of conventional Zn forms, Zn nanoparticles and novel Zn-foliar formulations. We examine the foliar application strategies and the attained final concentration of grain Zn. We propose a conceptual model for the response of grain Zn biofortification of wheat to foliar Zn application rates. This review discusses some physiological aspects of transportation of foliarly applied Zn that need further investigation. Finally, we explore the prospects of engineering foliar nano-formulations that could effectively overcome the physicochemical barrier to delivering Zn to wheat grains.
Narrative abilities in individuals with Down syndrome: single case-profiles
Authors: Neitzel Isabel
Published: October 2023

Introduction

Narrative abilities are an important part of our everyday lives and social interaction with others. Nevertheless, narration is a complex ability influenced by language and cognition. This makes it difficult for individuals with language and cognitive impairment, such as in children and adolescents with Down syndrome. Previous studies have shown distinct narrative impairments in individuals with Down syndrome; nevertheless, this research was based on overall group means in most cases. To identify individual strengths and weaknesses and to draw conclusions for speech and language therapy, the narrative profile of every participant should be considered equally. Following this approach, the current study aims to describe single case narrative profiles in individuals with Down syndrome.

Methods

The narrative transcripts of 28 children and adolescents with Down syndrome (aged 10;0–20;1), based on a non-verbal picture book, were rated using the Narrative Scoring Scheme across seven macro- and microstructural categories. Point scores across the whole group are displayed – nevertheless, the paper specifically addresses the individual narrative profiles of the participants. The participants could be assigned to narrative profile groups which show different characteristics, strengths and weaknesses. Group comparisons and correlations were computed for the relation to language abilities (especially vocabulary) and nonverbal cognitive abilities.

Results

The results of the two profile groups with minimal and developing narrative skills differ significantly not only concerning narrative outcomes in the Narrative Scoring Scheme but also for language abilities and developmental stage of nonverbal cognition. Individuals that show floor effects in narrative abilities are characterized by an overall weakness in language and cognition. In contrast, a group of approximately equal size shows distinct strengths in their narrative profiles which are in line with their vocabulary strengths, MLU and nonverbal cognition.

Discussion

The current study uses a new approach to identify individual narrative profiles in a group of individuals with Down syndrome. The results of the investigation underline the existence of narrative impairments in many individuals with Down syndrome but also point to individual strengths of the participants. Furthermore, the study outcomes suggest that narrative abilities might be representative for overall language and cognition in individuals with Down syndrome. However, intervention studies addressing narration are missing.
Assessment of users’ behavior in Lithuanian online communities
Authors: Skarzauskiene Aelita , Mačiulienė Monika
Published: October 2023

Introduction

Online communities are gaining importance in modern society by actively structuring public opinion and initiating discussions about various socio-economical issues. As information and communication technologies advance, the online communities are confronted with novel technological and societal hurdles (the spread of misinformation, lack of active participation). To boost their efficacy and productivity, it’s crucial to enhance our understanding of user behavior, communication avenues and potential future trends of development.

Objective

Online platforms serve a function beyond simply sharing information or knowledge; they act as influential social networks affecting various societal sectors, including politics, culture and the economy. There is a need to recognize online communities not as static entities, but as dynamic, evolving systems of collective intelligence.

Methods

A representative quantitative study was carried out between 1 to 30 of October 2022 through direct, in-person interviews conducted at the respondent’s residence (known as an Omnibus survey). The sample of respondents is representative of the entire population of Lithuania regarding essential socio-demographic characteristics. By thoroughly analyzing data gathered from a comprehensive quantitative study, the study raises awareness of the issues surrounding online communities, while also shedding light on social networking behavior within these virtual spaces.

Discussion

Despite the multitude of challenges inherent to virtual communication, there remains a significant knowledge gap in comprehending general user behavior within these online communities. The current research aims to bridge this gap by investigating user behavior in Lithuanian online communities.
Association between COVID-19 vaccination and critical outcomes among older adults with dementia: a comparative cohort study
Authors: Radomyslsky Zorian , Kivity Sara , Lidar Shira , Bentur Netta , Korn Liat , Nissanholtz-Gannot Rachel , Sternberg Shelley , Halevi Hochwald Inbal , Reges Orna , Alon Yaniv , Saban Mor
Published: October 2023

Background

As COVID-19 vaccines became available, understanding their potential benefits in vulnerable populations has gained significance. This study explored the advantages of COVID-19 vaccination in individuals with cognitive disorders by analyzing health-related variables and outcomes.

Methods

A prospective cohort study analyzed electronic medical records of 25,733 older adults with cognitive disorders and 65,544 older adults without cognitive disorders from March 2020 to February 2022. COVID-19 vaccination status was the primary exposure variable, categorized as fully vaccinated or unvaccinated. The primary outcomes measured were all-cause mortality and hospitalization rates within 14 and 400 days post-vaccination. Data on vaccination status, demographics, comorbidities, testing history, and clinical outcomes were collected from electronic health records. The study was ethically approved by the relevant medical facility’s Institutional Review Board (0075-22-MHS).

Results

Vaccinated individuals had significantly lower mortality rates in both groups. In the research group, the mortality rate was 52% (n = 1852) for unvaccinated individuals and 7% (n = 1,241) for vaccinated individuals (p < 0.001). Similarly, in the control group, the mortality rate was 13.58% (n = 1,508) for unvaccinated individuals and 1.85% (n = 936) for vaccinated individuals (p < 0.001), despite higher COVID-19 positivity rates. In the research group, 30.26% (n = 1,072) of unvaccinated individuals tested positive for COVID-19, compared to 37.16% (n = 6,492) of vaccinated individuals (p < 0.001). In the control group, 17.31% (n = 1922) of unvaccinated individuals were COVID-19 positive, while 37.25% (n = 18,873) of vaccinated individuals tested positive (p < 0.001). Vaccination also showed potential benefits in mental health support. The usage of antipsychotic drugs was lower in vaccinated individuals (28.43%, n = 4,967) compared to unvaccinated individuals (37.48%, n = 1,328; 95% CI [0.92–1.28], p < 0.001). Moreover, vaccinated individuals had lower antipsychotic drug prescription rates (23.88%, n = 4,171) compared to unvaccinated individuals (27.83%, n = 968; 95% CI [−1.02 to −0.63], p < 0.001). Vaccination appeared to have a positive impact on managing conditions like diabetes, with 38.63% (n = 6,748) of vaccinated individuals having diabetes compared to 41.55% (n = 1,472) of unvaccinated individuals (95% CI [0.24, 0.48], p < 0.001).

Discussion

The findings highlight the importance of vaccination in safeguarding vulnerable populations during the pandemic and call for further research to optimize healthcare strategies for individuals with cognitive disorders.
First impressions of a financial AI assistant: differences between high trust and low trust users
Authors: Schreibelmayr Simon , Moradbakhti Laura , Mara Martina
Published: October 2023

Calibrating appropriate trust of non-expert users in artificial intelligence (AI) systems is a challenging yet crucial task. To align subjective levels of trust with the objective trustworthiness of a system, users need information about its strengths and weaknesses. The specific explanations that help individuals avoid over- or under-trust may vary depending on their initial perceptions of the system. In an online study, 127 participants watched a video of a financial AI assistant with varying degrees of decision agency. They generated 358 spontaneous text descriptions of the system and completed standard questionnaires from the Trust in Automation and Technology Acceptance literature (including perceived system competence, understandability, human-likeness, uncanniness, intention of developers, intention to use, and trust). Comparisons between a high trust and a low trust user group revealed significant differences in both open-ended and closed-ended answers. While high trust users characterized the AI assistant as more useful, competent, understandable, and humanlike, low trust users highlighted the system's uncanniness and potential dangers. Manipulating the AI assistant's agency had no influence on trust or intention to use. These findings are relevant for effective communication about AI and trust calibration of users who differ in their initial levels of trust.