bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring food insecurity and multimorbidity in Indian socially disadvantaged people: cross-sectional findings from LASI, 2017–18
Authors: Ansari Salmaan , Anand Abhishek , Singh Shalini , Hossain Babul
Published: June 2023

Objectives

The present study aimed to examine the association of multimorbidity status with food insecurity among disadvantaged groups such as Scheduled Castes (SCs), Scheduled Tribes (STs), and Other Backward Class (OBCs) in India.

Method

The data for this study was derived from the first wave of the Longitudinal Ageing Study in India (LASI),2017–18, focusing on 46,953 individuals aged 45 years and over who belong to SCs, STs, and OBCs groups. Food insecurity was measured based on the set of five questions developed by the Food and Nutrition Technical Assistance Program (FANTA). Bivariate analysis was performed to examine the prevalence of food insecurity by multimorbidity status along with socio-demographic and health-related factors. Multivariable logistic regression analysis and interaction models were used.

Results

The overall prevalence of multimorbidity was about 16% of the study sample. The prevalence of food insecurity was higher among people with multimorbidity compared to those without multimorbidity. Unadjusted and adjusted models suggested that people with multimorbidity were more likely to be food insecure than people without multimorbidity. While middle-aged adults with multimorbidity and men with multimorbidity had a higher risk of food insecurity.

Conclusion

The findings of this study suggest an association between multimorbidity and food insecurity among socially disadvantaged people in India. Middle-aged adults experiencing food insecurity tend to reduce the quality of their diet and consume a few low-cost, nutritionally deficient meals to maintain caloric intake, putting them again at risk for several negative health outcomes. Therefore, strengthening disease management could reduce food insecurity in those facing multimorbidity.
Multi-institutional survey of antiemetic therapy in lung cancer patients treated with carboplatin in Hokushin region
Authors: Ide Takayuki , Nishino Yoshikazu , Takiguchi Tomoya , Kanda Shintaro , Otsuki Kengo , Hayashi Ryuji , Yasumoto Kazuo , Hirono Yasuo , Makino Tomoe , Yano Seiji , Koizumi Tomonobu
Published: June 2023

Objective

Appropriate monitoring and management of chemotherapy-induced nausea and vomiting (CINV) with prophylactic antiemetics is important for cancer patients. This study was performed to validate the clinical practice of antiemetic use with carboplatin-based chemotherapy in lung cancer patients in the Hokushin region (Toyama, Ishikawa, Fukui, and Nagano prefectures), Japan.

Methods

We surveyed retrospective data of newly diagnosed and registered lung cancer patients initially treated with carboplatin-based chemotherapy in 21 principal hospitals in the Hokushin region linked with health insurance claims data between 2016 and 2017.

Results

A total of 1082 lung cancer patients (861 [79.6%] men, 221 [20.4%] women; median age 69.4 years [range, 33–89 years]). All patients received antiemetic therapy, with 613 (56.7%) and 469 patients (43.3%) receiving 5-hydroxytryptamine-3 receptor antagonist/dexamethasone double regimen and 5-hydroxytryptamine-3 receptor antagonist/dexamethasone/neurokinin-1 receptor antagonist triple regimen, respectively. However, the rates of double regimen and use of palonosetron were higher in Toyama and Fukui prefectures. Thirty-nine patients (3.6%) changed from double to triple regimen, while 41 patients (3.8%) changed from triple to double regimen after the second cycle, but six of these returned to triple antiemetics in subsequent cycles.

Conclusion

Adherence to antiemetic guidelines in clinical practice was high in Hokushin region. However, rates of double and triple antiemetic regimens differed between the four prefectures. Simultaneous analysis of nationwide registry and insurance data was valuable for evaluating and comparing the differences in the status of antiemesis and management.
Deciphering the role of Saliva in COVID 19: A global cross-sectional study on the knowledge, awareness and perception among dentists
Authors: Kritika Selvakumar , Mahalaxmi Sekar , Srinivasan N , Krithikadatta Jogikalmat
Published: June 2023

Objectives

The global pandemic outbreak of the coronavirus has instilled the quest amongst researchers on the expedited need for the early detection of viral load. Saliva is a complex oral biological fluid which not only causes the disease transmission but can be an effective alternative sample for detection of SARS-CoV2. This provides an ideal opportunity for dentists to be the frontline healthcare professionals who can collect the salivary samples; however the awareness of this amongst dentists is uncertain. Hence the aim of this survey was to evaluate the knowledge, perception and awareness of the role of saliva in detecting the SARS-CoV2 among dentists worldwide.

Methods

The online questionnaire comprising of 19 questions was shared to 1100 dentists worldwide and a total of 720 responses was collected. The data was tabulated, statistically analysed using the non- parametric Kruskal-Wallis test (p < 0.05). Based on the principal component analysis, 4 components (knowledge about virus transmission, perception about SARS-CoV2 virus, awareness on the sample collection and knowledge about prevention of the virus) were obtained which was compared with the 3 independent variables (years of clinical experience, occupation and region).

Results

A statistically significant difference was observed in the awareness quotient amongst the dentists with 0–5 years and greater than 20 years of clinical experience. In terms of the occupation, a significant difference was noted when comparing the postgraduate students to practitioners knowledge about the virus transmission. A highly significant difference was seen on comparing academicians and postgraduate students and also between academicians and practitioners. No significant difference was evidenced amongst the different regions, however the mean score was in the range of 3-3.44.

Conclusion

This survey highlights the deficiency in the knowledge, perception and awareness among dentists worldwide.
Therapeutic efficacy of sorafenib and plant-derived phytochemicals in human colorectal cancer cells
Authors: Bahman Abdulmajeed , Abaza Mohamed-Salah , Khoushaish Sarah , Al-Attiyah Rajaa J.
Published: June 2023

Background

The present study aimed to investigate the sequence-dependent anticancer effects of combined treatment with sorafenib (Sora), a Food and Drug Administration-approved multikinase inhibitor drug, and plant-derived phytochemicals (PPCs) on human colorectal cancer (CRC) cell growth, and proteins associated with the control of cell cycle and apoptosis.

Methods

The cytotoxic effects of 14 PPCs on CRL1554 fibroblast cells were determined using an MTT assay. Moreover, the cytotoxicity of Sora, PPCs, and a combination of both on CRC cells were also investigated. Cell cycle analysis was performed using flow cytometry, and cell apoptosis was investigated using DNA fragmentation, Annexin V/propidium iodide double staining, and mitochondrial membrane potential analyses. The cell cycle- and apoptosis-associated protein expression levels were analysed using western blotting.

Results

Based on their low levels of cytotoxicity in CRL1554 cells at ≤ 20%, curcumin, quercetin, kaempferol, and resveratrol were selected for use in subsequent experiments. The combined treatment of sora and PPCs caused levels of CRC cytotoxicity in a dose-, cell type-, and schedule-dependent manner. Moreover, the combined treatment of CRC cells arrested cell growth at the S and G2/M phases, induced apoptotic cell death, caused extensive mitochondrial membrane damage, and altered the expression of the cell cycle and apoptotic proteins.

Conclusions

Results of the present study highlighted a difference in the level of sora efficacy in CRC cells when combined with PPCs. Further in vivo and clinical studies using the combined treatment of sora and PPCs are required to determine their potential as a novel therapeutic strategy for CRCs.
Systematic review of economic evaluations of aromatase inhibitors in estrogen receptor-positive breast cancer: quality evaluation
Authors: Althuwaibi Maha F. , Fernandez-Garcia Cristina , Hayes Louise , McNally Richard , Coughlan Diarmuid
Published: June 2023

Background

Breast cancer (BC) is a leading cause of premature death in women and the most expensive malignancy to treat. Since the introduction of targeted therapies has resulted in changes to BC therapy practices, health economic evaluations have become more important in this area. Taking generic medications, Aromatase Inhibitors (AIs), as a case study, we conducted a systematic review of the recent economic evaluations of AIs for estrogen receptor-positive breast cancer patients and evaluated the quality of these health economic studies.

Objective

To systematically review and examine the quality of the available economic studies of AIs in estrogen receptor-positive breast cancer.

Methods

A literature search was performed using six relevant databases (MEDLINE, Embase, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, NHS Economic Evaluation Database, and SCOPUS) from January 2010 to July 2021. All economic studies were independently assessed by two reviewers using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist to evaluate the quality of the economic evaluations. This systematic review is registered in the PROSPERO database. To compare the different currencies used in these studies, all costs were converted to international dollars (2021).

Results

A total of eight studies were included in the review; six (75%) were performed from the healthcare providers’ perspective. They were conducted in seven different countries, and all were model-based analyses using Markov models. Six (75%) considered both Quality Adjusted Life Years (QALYs) and Life Years (LY) outcomes, and all costs were derived from national databases. When compared to tamoxifen, AIs were generally cost-effective in postmenopausal women. Only half of the studies addressed the increased mortality following adverse events, and none mentioned medication adherence. For the quality assessment, six studies fulfilled 85% of the CHEERS checklist requirements and are deemed good quality.

Conclusion

AIs are generally considered cost-effective compared to tamoxifen in estrogen receptor-positive breast cancer. The overall quality of the included studies was between high and average but characterizing heterogeneity, and distributional effects should be considered in any future economic evaluation studies of AIs. Studies should include adherence and adverse effects profiles to provide evidence to facilitate decision-making among policymakers.
Multiple and diversified transposon lineages contribute to early and recent bivalve genome evolution
Authors: Martelossi Jacopo , Nicolini Filippo , Subacchi Simone , Pasquale Daniela , Ghiselli Fabrizio , Luchetti Andrea
Published: June 2023

Background

Transposable elements (TEs) can represent one of the major sources of genomic variation across eukaryotes, providing novel raw materials for species diversification and innovation. While considerable effort has been made to study their evolutionary dynamics across multiple animal clades, molluscs represent a substantially understudied phylum. Here, we take advantage of the recent increase in mollusc genomic resources and adopt an automated TE annotation pipeline combined with a phylogenetic tree-based classification, as well as extensive manual curation efforts, to characterize TE repertories across 27 bivalve genomes with a particular emphasis on DDE/D class II elements, long interspersed nuclear elements (LINEs), and their evolutionary dynamics.

Results

We found class I elements as highly dominant in bivalve genomes, with LINE elements, despite less represented in terms of copy number per genome, being the most common retroposon group covering up to 10% of their genome. We mined 86,488 reverse transcriptases (RVT) containing LINE coming from 12 clades distributed across all known superfamilies and 14,275 class II DDE/D-containing transposons coming from 16 distinct superfamilies. We uncovered a previously underestimated rich and diverse bivalve ancestral transposon complement that could be traced back to their most recent common ancestor that lived ~ 500 Mya. Moreover, we identified multiple instances of lineage-specific emergence and loss of different LINEs and DDE/D lineages with the interesting cases of CR1- Zenon, Proto2, RTE-X, and Academ elements that underwent a bivalve-specific amplification likely associated with their diversification. Finally, we found that this LINE diversity is maintained in extant species by an equally diverse set of long-living and potentially active elements, as suggested by their evolutionary history and transcription profiles in both male and female gonads.

Conclusions

We found that bivalves host an exceptional diversity of transposons compared to other molluscs. Their LINE complement could mainly follow a “stealth drivers” model of evolution where multiple and diversified families are able to survive and co-exist for a long period of time in the host genome, potentially shaping both recent and early phases of bivalve genome evolution and diversification. Overall, we provide not only the first comparative study of TE evolutionary dynamics in a large but understudied phylum such as Mollusca, but also a reference library for ORF-containing class II DDE/D and LINE elements, which represents an important genomic resource for their identification and characterization in novel genomes.
Rapid kidney function decline and increased risk of heart failure in patients with type 2 diabetes: findings from the ACCORD cohort
Authors: Bueno Junior Carlos Roberto , Bano Arjola , Tang Yaling , Sun Xiuqin , Abate Alex , Hall Elizabeth , Mitri Joanna , Morieri Mario Luca , Shah Hetal , Doria Alessandro
Published: June 2023

Background

Impaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D, independent of baseline kidney function, albuminuria, and other HF predictors.

Methods

Included in the study were 7,539 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with baseline urinary albumin-to-creatinine ratio (UACR) data, who had completed 4 years of follow-up and had ≥ 3 eGFR measurements during that period (median eGFR/year = 1.9, IQR 1.7–3.2). The association between rapid kidney function decline (eGFR loss ≥ 5 ml/min/1.73 m2/year) and odds of HF hospitalization or HF death during the first 4 years of follow-up was estimated by logistic regression. The improvement in risk discrimination provided by adding rapid kidney function decline to other HF risk factors was evaluated as the increment in the area under the Receiving Operating Characteristics curve (ROC AUC) and integrated discrimination improvement (IDI).

Results

Over 4 years of follow-up, 1,573 participants (20.9%) experienced rapid kidney function decline and 255 (3.4%) experienced a HF event. Rapid kidney function decline was associated with a ~ 3.2-fold increase in HF odds (3.23, 95% CI, 2.51–4.16, p < 0.0001), independent of baseline CVD history. This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline as well as at censoring (3.74; 95% CI 2.63–5.31). Adding rapid kidney function decline during follow-up to other clinical predictors (WATCH-DM score, eGFR, and UACR at study entry and end of follow-up) improved HF risk classification (ROC AUC = + 0.02, p = 0.027; relative IDI = + 38%, p < 0.0001).

Conclusions

In patients with T2D, rapid kidney function decline is associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF risk estimation in T2D.
Prognostic impacts of diabetes status and lipoprotein(a) levels in patients with ST-segment elevation myocardial infarction: a prospective cohort study
Authors: Li Nan , Zhou Jinying , Chen Runzhen , Zhao Xiaoxiao , Li Jiannan , Zhou Peng , Liu Chen , Chen Yi , Wang Ying , Song Li , Yan Shaodi , Zhao Hanjun , Yan Hongbing
Published: June 2023

Objects

This study aimed to investigate the impact of lipoprotein(a) [Lp(a)] levels on the prognosis of Chinese patients with ST-segment elevation myocardial infarction (STEMI), and to explore if the impact may differ in the diabetes mellitus (DM) and nonDM groups.

Methods

Between March 2017 and January 2020, 1543 patients with STEMI who underwent emergency percutaneous coronary intervention (PCI) were prospectively recruited. The primary outcome was a composite of all-cause death, MI recurrence (reMI), and stroke, known as major adverse cardiovascular events (MACE). Analyses involving the Kaplan–Meier curve, Cox regression, and restricted cubic spline (RCS) were conducted.

Results

During the 1446-day follow-up period, 275 patients (17.8%) experienced MACEs, including 141 with DM (20.8%) and 134 (15.5%) without DM. As for the DM group, patients with Lp(a) ≥ 50 mg/dL showed an apparently higher MACE risk compared to those with Lp(a) < 10 mg/dL (adjusted hazard ratio [HR]: 1.85, 95% confidence interval [CI]:1.10–3.11, P = 0.021). The RCS curve indicates that the HR for MACE appeared to increase linearly with Lp(a) levels exceeding 16.9 mg/dL. However, no similar associations were obtained in the nonDM group, with an adjusted HR value of 0.57 (Lp(a) ≥ 50 mg/dL vs. < 10 mg/dL: 95% CI 0.32–1.05, P = 0.071). Besides, compared to patients without DM and Lp(a) ≥ 30 mg/dL, the MACE risk of patients in the other three groups (nonDM with Lp(a) < 30 mg/dL, DM with Lp(a) < 30 mg/dL, and DM with Lp(a) ≥ 30 mg/dL) increased to 1.67-fold (95% CI 1.11–2.50, P = 0.013), 1.53-fold (95% CI 1.02–2.31, P = 0.041), and 2.08-fold (95% CI 1.33–3.26, P = 0.001), respectively.

Conclusions

In this contemporary STEMI population, high Lp(a) levels were linked to an increased MACE risk, and very high Lp(a) levels (≥ 50 mg/dL) significantly indicated poor outcomes in patients with DM, while not for those without DM.

Trial registration: clinicaltrials.gov NCT: 03593928
Comparing field-collected versus remotely-sensed variables to model malaria risk in the highlands of western Uganda
Authors: Hollingsworth Brandon D. , Sandborn Hilary , Baguma Emmanuel , Ayebare Emmanuel , Ntaro Moses , Mulogo Edgar M. , Boyce Ross M.
Published: June 2023

Background

Malaria risk is not uniform across relatively small geographic areas, such as within a village. This heterogeneity in risk is associated with factors including demographic characteristics, individual behaviours, home construction, and environmental conditions, the importance of which varies by setting, making prediction difficult. This study attempted to compare the ability of statistical models to predict malaria risk at the household level using either (i) free easily-obtained remotely-sensed data or (ii) results from a resource-intensive household survey.

Methods

The results of a household malaria survey conducted in 3 villages in western Uganda were combined with remotely-sensed environmental data to develop predictive models of two outcomes of interest (1) a positive ultrasensitive rapid diagnostic test (uRDT) and (2) inpatient admission for malaria within the last year. Generalized additive models were fit to each result using factors from the remotely-sensed data, the household survey, or a combination of both. Using a cross-validation approach, each model’s ability to predict malaria risk for out-of-sample households (OOS) and villages (OOV) was evaluated.

Results

Models fit using only environmental variables provided a better fit and higher OOS predictive power for uRDT result (AIC = 362, AUC = 0.736) and inpatient admission (AIC = 623, AUC = 0.672) compared to models using household variables (uRDT AIC = 376, Admission AIC = 644, uRDT AUC = 0.667, Admission AUC = 0.653). Combining the datasets did not result in a better fit or higher OOS predictive power for uRDT results (AIC = 367, AUC = 0.671), but did for inpatient admission (AIC = 615, AUC = 0.683). Household factors performed best when predicting OOV uRDT results (AUC = 0.596) and inpatient admission (AUC = 0.553), but not much better than a random classifier.

Conclusions

These results suggest that residual malaria risk is driven more by the external environment than home construction within the study area, possibly due to transmission regularly occurring outside of the home. Additionally, they suggest that when predicting malaria risk the benefit may not outweigh the high costs of attaining detailed information on household predictors. Instead, using remotely-sensed data provides an equally effective, cost-efficient alternative.
Pharmacologic inhibition of IL11/STAT3 signaling increases MHC-I expression and T cell infiltration
Authors: Xiong Wenjun , Chen Yuehong , Zhang Chaoting , Li Jin , Huang Haipeng , Zhu Yu , Deng Guangxu , Cheng Junhong , Lin Yixiong , Shi Zhimin , Mou Tingyu
Published: June 2023

Background

Recent studies have discovered an emerging role of IL11 in various colitis-associated cancers, suggesting that IL11 mainly promotes tumor cell survival and proliferation in regulating tumorigenesis. Herein we aimed to reveal a novel function of IL-11 through STAT3 signaling in regulating tumor immune evasion.

Methods

AOM/DSS model in Il11−/− and Apcmin/+/Il11−/− mice were used to detect tumor growth and CD8+ T infiltration. STAT1/3 phosphorylation and MHC-I, CXCL9, H2-K1 and H2-D1 expression were detected in MC38 cells and intestine organoids treated with/without recombinant IL11 to explore effect of IL11/STAT3 signaling, with IL11 mutein used to competitively inhibit IL11 and rescue inhibited STAT1 activation. Correlation between IL11 and CD8+ T infiltration was analyzed using TIMER2.0 website. IL11 expression and survival prognosis was analyzed in clinical data of patient cohort from Nanfang Hospital.

Results

IL11 is highly expressed in CRC and indicates unfavorable prognosis. IL11 knockout increased CD8+ T cell infiltration and reduced intestinal and colon formation. Tumors were significantly suppressed while MHC-I and CXCL9 expression for CD8+ T infiltration were remarkably increased in the tumor tissues of Apcmin/+/Il11−/− mice or Il11−/− mice induced by AOM/DSS. IL11/STAT3 signaling downregulated MHC-I and CXCL9 by inhibiting IFNγ-induced STAT1 phosphorylation. IL11 mutein competitively inhibit IL11 to upregulate CXCL9 and MHC-I in tumor and attenuated tumor growth.

Conclusions

This study ascribes for a new immunomodulatory role for IL11 during tumor development that is amenable to anti-cytokine based therapy of colon cancer.
Implementation and scale-up of a single-visit, screen-and-treat approach with thermal ablation for sustainable cervical cancer prevention services: a protocol for a stepped-wedge cluster randomized trial in Kenya
Authors: Shin Michelle B. , Oluoch Lynda Myra , Barnabas Ruanne V. , Baynes Colin , Fridah Harriet , Heitner Jesse , Kerubo Mary Bernadette , Ngure Kenneth , Pinder Leeya F. , Thomas Katherine K. , Mugo Nelly Rwamba , Gimbel Sarah
Published: June 2023

Background

An important cervical cancer prevention strategy in low- and middle-income countries (LMICs) has been single-visit screen-and-treat (SV-SAT) approach, using visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy to manage precancerous lesions. While SV-SAT with VIA and cryotherapy have established efficacy, its population level coverage and impact on reducing cervical cancer burden remains low. In Kenya, the estimated cervical cancer screening uptake among women aged 30–49 is 16% and up to 70% of screen-positive women do not receive treatment. Thermal ablation for treatment of precancerous lesions of the cervix is recommended by the World Health Organization and has the potential to overcome logistical challenges associated with cryotherapy and facilitate implementation of SV-SAT approach and increase treatment rates of screen-positive women. In this 5-year prospective, stepped-wedge randomized trial, we plan to implement and evaluate the SV-SAT approach using VIA and thermal ablation in ten reproductive health clinics in central Kenya.

Methods

The study aims to develop and evaluate implementation strategies to inform the national scale-up of SV-SAT approach with VIA and thermal ablation through three aims: (1) develop locally tailored implementation strategies using multi-level participatory method with key stakeholders (patient, provider, system-level), (2) implement SV-SAT approach with VIA and thermal ablation and evaluate clinical and implementation outcomes, and (3) assess the budget impact of SV-SAT approach with VIA and thermal ablation compared to single-visit, screen-and-treat method using cryotherapy.

Discussion

Our findings will inform national scale-up of the SV-SAT approach with VIA and thermal ablation. We anticipate that this intervention, along with tailored implementation strategies will enhance the adoption and sustainability of cervical cancer screening and treatment compared to the standard of care using cryotherapy.

Trial registration

NCT05472311.
Validation of a QTL associated with resistance to Vibrio anguillarum in rainbow trout (Oncorhynchus mykiss)
Authors: Karami Asma Mohammad , Marana Moonika Haahr , Mathiessen Heidi , Dalsgaard Inger , Nielsen Torben Fejer , Kania Per Walter , Buchmann Kurt
Published: June 2023

Vibriosis is a bacterial disease in fish caused by the Gram negative bacterium Vibrio anguillarum with severe impact on rainbow trout (Oncorhynchus mykiss) farming. Sustainable control methods should be developed and we here show that marker assisted selective breeding of fish naturally resistant to the disease is feasible. We have validated the use of a single nucleotide polymorphism (SNP) marker SNP AX-89,945,921 (QTL on chromosome 21). The QTL was previously found associated with resistance to vibriosis and described following a genome wide association analysis (GWAS) of trout exposed to the bacterium. For this validation spawners were genotyped by use of the 57 K Axiom®Trout Microarray (Affymetrix) and homozygous male fish carrying the allele with the SNP AX-89,945,921 were then selected and used to fertilize eggs from outbred female trout resulting in fish all carrying the SNP (QTL-fish). Control fish (non-QTL fish) were produced by fertilizing the same batch of eggs by use of male parents negative for the SNP. The fish were exposed in freshwater to V. anguillarum (water bath infection) at 19 C°. A total of 900 fish were challenged in a common garden set-up in triplicate. A bacterial solution of V. anguillarum (serotype O1) was added to each of three freshwater fish tanks, each with 150 QTL and 150 non-QTL fish. Fish were tagged by tail fin cut (upper/lower) to discern the two groups, whereafter fish were monitored around the clock to detect disease signs and remove moribund fish. Clinical vibriosis developed within two days in non-QTL-fish (overall morbidity of 70%). QTL fish developed clinical signs later and the morbidity was significantly lower and did not reach 50%. Rainbow trout farming may benefit from using the QTL associated with higher resistance towards vibriosis. The effect may be optimized in the future by use of both male and female parents homozygous for the marker allele.
Interval-valued bipolar fuzzy line graphs
Authors: Tola Keneni Abera , Repalle V. N. Srinivasa Rao , Ashebo Mamo Abebe
Published: June 2023

Objectives

The notion of Bipolarity based on positive and negative outcomes. It is well known that bipolar models give more precision, flexibility, and compatibility to the system as compared to the classical models and fuzzy models. A bipolar fuzzy graph(BFG) provides more flexibility while modeling human thinking as compared with a fuzzy graph, and an interval valued bipolar fuzzy graph(IVBFG) has numerous applications where the real-life problem are time dependent and there is a network structure complexity. The aim of this paper is to introduce an interval-valued bipolar line fuzzy graph(IVBFLG).

Result

In this paper, we have proposed the notion of an IVBFLG and some of its characterizations. Also, some propositions and theorems related to an IVIFLGs are developed and proved. Furthermore, isomorphism between two IVIFLGs toward their IVIFGs was determined and verified. As a result, we derive a necessary and sufficient condition for an IVBFG to be isomorphic to its corresponding IVBFLG and some remarkable properties like degree, size, order, regularity, strength, and completeness of an IVBFLGs have been investigated, and the proposed concepts are illustrated with the examples.
Leishmanicidal and immunomodulatory activities of the formononetin (a natural isoflavone) against Leishmania tropica
Authors: Mahmoudvand Hossein , Khalaf Amal Khudair , Rajabi Pouya Zareh , Karbasian Nooshin , Ghasemian Yadegari Javad
Published: June 2023

Objective

This work aimed to examine the leishmanicidal, cellular mechanisms and cytotoxicity effects of formononetin (FMN), a natural isoflavone, against Leishmania tropica. We used the MTT assay to determine the leishmanicidal effects of FMN against promastigotes and its cytotoxicity effects on J774-A1 macrophage cells. The Griess reaction assay and quantitative real-time PCR were used to determine the nitric oxide (NO) and the mRNA expression levels of IFN-γ and iNOS in infected J774-A1 macrophage cells.

Results

FMN significantly (P < 0.001) decreased the viability and number of promastigotes and amastigotes forms. The 50% inhibitory concentrations value for FMN and glucantime was 9.3 and 14.3 µM for promastigote and amastigote, respectively. We found that the macrophages exposed with FMN especially at concentrations of 1/2 IC50 and IC50 significantly activated the NO release and the mRNA expression levels of IFN-γ, iNOS. The findings of the current research showed the favorable antileishmanial effects formononetin, a natural isoflavone, against various stages of L. tropica through inhibition of infectivity rate of macrophage cells and triggering the NO production and cellular immunity. However, supplementary works are essential to evaluate the ability and safety of FMN in animal model before use in the clinical phase.
Differentially expressed transcripts of Tetracapsuloides bryosalmonae (Cnidaria) between carrier and dead-end hosts involved in key biological processes: novel insights from a coupled approach of FACS and RNA sequencing
Authors: Shivam Saloni , Ertl Reinhard , Sexl Veronika , El-Matbouli Mansour , Kumar Gokhlesh
Published: June 2023

Tetracapsuloides bryosalmonae is a malacosporean endoparasite that infects a wide range of salmonids and causes proliferative kidney disease (PKD). Brown trout serves as a carrier host whereas rainbow trout represents a dead-end host. We thus asked if the parasite adapts to the different hosts by changing molecular mechanisms. We used fluorescent activated cell sorting (FACS) to isolate parasites from the kidney of brown trout and rainbow trout following experimental infection with T. bryosalmonae. The sorted parasite cells were then subjected to RNA sequencing. By this approach, we identified 1120 parasite transcripts that were expressed differentially in parasites derived from brown trout and rainbow trout. We found elevated levels of transcripts related to cytoskeleton organisation, cell polarity, peptidyl-serine phosphorylation in parasites sorted from brown trout. In contrast, transcripts related to translation, ribonucleoprotein complex biogenesis and subunit organisation, non-membrane bounded organelle assembly, regulation of protein catabolic process and protein refolding were upregulated in rainbow trout-derived parasites. These findings show distinct molecular adaptations of parasites, which may underlie their distinct outcomes in the two hosts. Moreover, the identification of these differentially expressed transcripts may enable the identification of novel drug targets that may be exploited as treatment against T. bryosalmonae. We here also describe for the first time how FACS based isolation of T. bryosalmonae cells from infected kidney of fish fosters research and allows to define differentially expressed parasite transcripts in carrier and dead-end fish hosts.
A machine learning-based model for a dose point kernel calculation
Authors: Scarinci Ignacio , Valente Mauro , Pérez Pedro
Published: June 2023

Purpose

Absorbed dose calculation by kernel convolution requires the prior determination of dose point kernels (DPK). This study reports on the design, implementation, and test of a multi-target regressor approach to generate the DPKs for monoenergetic sources and a model to obtain DPKs for beta emitters.

Methods

DPK for monoenergetic electron sources were calculated using the FLUKA Monte Carlo (MC) code for many materials of clinical interest and initial energies ranging from 10 to 3000 keV. Regressor Chains (RC) with three different coefficients regularization/shrinkage models were used as base regressors. Electron monoenergetic scaled DPKs (sDPKs) were used to assess the corresponding sDPKs for beta emitters typically used in nuclear medicine, which were compared against reference published data. Finally, the beta emitters sDPK were applied to a patient-specific case calculating the Voxel Dose Kernel (VDK) for a hepatic radioembolization treatment with$$^{90}$$90Y.

Results

The three trained machine learning models demonstrated a promising capacity to predict the sDPK for both monoenergetic emissions and beta emitters of clinical interest attaining differences lower than$$10\%$$10%in the mean average percentage error (MAPE) as compared with previous studies. Furthermore, differences lower than$$7 \%$$7%were obtained for the absorbed dose in patient-specific dosimetry comparing against full stochastic MC calculations.

Conclusion

An ML model was developed to assess dosimetry calculations in nuclear medicine. The implemented approach has shown the capacity to accurately predict the sDPK for monoenergetic beta sources in a wide range of energy in different materials. The ML model to calculate the sDPK for beta-emitting radionuclides allowed to obtain VDK useful to achieve reliable patient-specific absorbed dose distributions required short computation times.
Predictive value of CHA2DS2VASC score for contrast-induced nephropathy after primary percutaneous coronary intervention for patients presenting with acute ST-segment elevation myocardial infarction
Authors: Samir Ahmad , Gabra Wafik , Alhossary Hossam , Bakhoum Sameh
Published: June 2023

Background

ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI) are at increased risk for contrast-induced nephropathy (CIN) than elective PCI procedures. Routine calculation of Mehran’s score is limited by its complexity and difficulty to memorize. This study evaluated CHA2DS2-VASc score predictive utility for CIN in STEMI patients before pPCI.

Results

Consecutive 500 acute STEMI patients presenting to two Egyptian pPCI centers were recruited. Exclusion criteria included cardiogenic shock or known severe renal impairment (baseline serum creatinine ≥ 3 mg/dL) or current or previous indication of hemodialysis. CHA2DS2VASC score, Mehran’s score, baseline estimated glomerular filtration rate (eGFR), contrast media volume (CMV) and CMV/eGFR ratio were collected for all patients. Post-pPCI CIN (defined as 0.5 mg/dL absolute increase or 25% relative increase of serum creatinine from baseline) and predictive accuracy of CHA2DS2VASC and Mehran’s scores were evaluated. CIN occurred in 35 (7%) of the study group. Values of CHA2DS2VASC score, Mehran’s score, baseline eGFR, CMV and CMV/eGFR ratio were significantly higher in those who developed CIN compared to those who did not. CHA2DS2VASC score, Mehran’s score and CMV/eGFR were found to be independent predictors for CIN (P < 0.001 for all). ROC curve analysis revealed that CHA2DS2VASC ≥ 4 had a superb predictive ability, comparable to Mehran’s score, for post-pPCI CIN.

Conclusions

Being practical, easily memorizable and applicable before proceeding to pPCI, routine CHA2DS2VASC score calculation in STEMI patients can effectively predict CIN risk and guide preventive and/or therapeutic interventions.
Normalized LST Is an Efficient Biomarker for Homologous Recombination Deficiency and Olaparib Response in Ovarian Carcinoma
Authors: Christinat Yann , Ho Liza , Clément Sophie , Genestie Catherine , Sehouli Jalid , Cinieri Saverio , Gonzalez Martin Antonio , Denison Ursula , Fujiwara Keiichi , Vergote Ignace , Tognon Germana , Hietanen Sakari , Ray-Coquard Isabelle , Pujade-Lauraine Eric , McKee Thomas A.
Published: June 2023

PURPOSE

The efficiency of the Myriad Homologous Recombination Deficiency (HRD) test to guide the use of poly (ADP-ribose) polymerase (PARP) inhibitors has been demonstrated in several phase III trials. However, a need exists for alternative clinically validated tests.

METHODS

A novel biomarker for HRD was developed using The Cancer Genome Atlas database and, as part of the ENGOT HRD European Initiative, applied to 469 samples from the PAOLA-1/ENGOT-ov25 trial. Results were compared with the Myriad myChoice Genomic Instability Score (GIS) with respect to the progression-free survival in the olaparib + bevacizumab and placebo + bevacizumab arms.

RESULTS

Analysis of the TCGA cohort revealed that a normalization of the number of large-scale state transitions by the number of whole-genome doubling events allows a better separation and classification of HRD samples than the GIS. Analysis of the PAOLA-1 samples, using the Geneva test (OncoScan + nLST), yielded a lower failure rate (27 of 469 v 59 of 469) and a hazard ratio of 0.40 (95% CI, 0.28 to 0.57) compared with 0.37 for Myriad myChoice (BRCAm or GIS+) in the nLST-positive samples. In patients with BRCAwt, the Geneva test identified a novel subpopulation of patients, with a favorable 1-year PFS (85%) but a poor 2-year PFS (30%) on olaparib + bevacizumab treatment.

CONCLUSION

The proposed test efficiently separates HRD-positive from HRD-negative patients, predicts response to PARP inhibition, and can be easily deployed in a clinical laboratory for routine practice. The performance is similar to the available commercial test, but its lower failure rate allows an increase in the number of patients who will receive a conclusive laboratory result.
Case of a Patient With Pancreatic Cancer With Sporadic Microsatellite Instability Associated With a BRAF Fusion Achieving Excellent Response to Immunotherapy
Authors: Heinrich Kathrin , Fischer Laura E. , De Toni Enrico N. , Markwardt Daniel , Roessler Daniel , Beyer Georg , Günther Michael , Ormanns Steffen , Klauschen Frederick , Kunz Wolfgang G. , Fröhling Stefan , Brummer Tilman , Heinemann Volker , Westphalen C. Benedikt
Published: June 2023

In this case report, we discuss a case of pancreatic cancer bearing a BRAF fusion, leading to MAPK activation, MLHph, and finally MSI.
Nicotinamide Adenine Dinucleotide in Aging Biology: Potential Applications and Many Unknowns
Authors: Bhasin Shalender , Seals Douglas , Migaud Marie , Musi Nicolas , Baur Joseph A
Published: June 2023

Recent research has unveiled an expansive role of NAD+ in cellular energy generation, redox reactions, and as a substrate or cosubstrate in signaling pathways that regulate health span and aging. This review provides a critical appraisal of the clinical pharmacology and the preclinical and clinical evidence for therapeutic effects of NAD+ precursors for age-related conditions, with a particular focus on cardiometabolic disorders, and discusses gaps in current knowledge. NAD+ levels decrease throughout life; age-related decline in NAD+ bioavailability has been postulated to be a contributor to many age-related diseases. Raising NAD+ levels in model organisms by administration of NAD+ precursors improves glucose and lipid metabolism; attenuates diet-induced weight gain, diabetes, diabetic kidney disease, and hepatic steatosis; reduces endothelial dysfunction; protects heart from ischemic injury; improves left ventricular function in models of heart failure; attenuates cerebrovascular and neurodegenerative disorders; and increases health span. Early human studies show that NAD+ levels can be raised safely in blood and some tissues by oral NAD+ precursors and suggest benefit in preventing nonmelanotic skin cancer, modestly reducing blood pressure and improving lipid profile in older adults with obesity or overweight; preventing kidney injury in at-risk patients; and suppressing inflammation in Parkinson disease and SARS-CoV-2 infection. Clinical pharmacology, metabolism, and therapeutic mechanisms of NAD+ precursors remain incompletely understood. We suggest that these early findings provide the rationale for adequately powered randomized trials to evaluate the efficacy of NAD+ augmentation as a therapeutic strategy to prevent and treat metabolic disorders and age-related conditions.
Homoverse
Authors: Khalip Jacques , Ricco John Paul
Published: June 2023

The editors’ introduction to this special issue of differences titled Syntax of Thought: Reading Leo Bersani describes the issue’s focus on the speculative importance of aesthetics in Leo Bersani’s scholarship, especially his attention to a “syntax of thought,” or the structural innovations of thinking, reading, and perception explored throughout his critical writings. The introduction also emphasizes Bersani’s ongoing attention to relationality through the aesthetic and how it contributed to his decades-long rethinking of sexuality, sociality, politics, and art.
Aestheticism
Authors: Rhodes John David
Published: June 2023

This essay considers Bersani and Dutoit’s alignment of passivity and the aesthetic in “Merde Alors,” their essay on Pier Paolo Pasolini’s film Salò. Passivity is a key strategy for the production of works of art and is key to understanding the mode of the aesthetic itself. The question of passivity appears elsewhere in Bersani’s work, and “Merde Alors”—in whole or in part—was republished at key moments in Bersani’s career. This essay gestures toward why “Merde Alors” has had such an interesting and prolific afterlife.
Assyrians
Authors: Rifkin Adrian
Published: June 2023

This essay argues that Leo Bersani’s immersion in a discipline of reading theoretical and psychoanalytic texts and literature with close critical attention effectively writes out his observations from an epistemology of being gay. His attention to visual materials is similarly acute and detailed, and the observed and the read fragment interfere with each other in a virtuosic demonstration of criticism that is both involved and detached. In this process, his writing refuses any illusion of the possibility of theoretical coherence as a purpose of his text. Rather, Bersani’s writing produces new queer knowledge as a collateral effect of who he was.
Bracket
Authors: Cohen Kris
Published: June 2023

In Leo Bersani’s essay “Sociality and Sexuality,” bracketing emerges as a critical procedure for sensing and for practicing nonsovereign forms of sociality. Following Foucault’s desire to discover modes of relation, forms of the homosexual, that do not yet have a world for their reception, Bersani brackets the literature on sociality and sexuality that has come before, including his own, which variously posits the homosexual and the queer as figures of radical negation. Averse to such recuperations of the sovereign self, Bersani’s bracketing instead makes space for the homoerotic as a set of fragile, experimental modes of relation in which the self is neither an enemy nor a heroic site of resistance.
Cage
Authors: McGlazer Ramsey
Published: June 2023

This essay studies figures of arrest and mobility, imprisonment and release, and “rigor and extravagance” in Leo Bersani’s writings. Focusing on The Forms of Violence, a study of late Assyrian sculpture coauthored with Ulysse Dutoit and first published in 1985, the essay at once follows and moves away from the book’s analysis of “a cage which imprisons nothing.” Asking what this analysis discloses and what it occludes, the essay turns briefly to the vast expansion of California’s carceral state that forms a historical backdrop for the book’s composition. The author reads The Forms of Violence as unseeing this expansion as well as the history of the institution that sustains Bersani and Dutoit’s reflections: the museum. Written as a tribute to Bersani, the essay attends to both his style and the movements of his thought.
Deconstruction
Authors: Brilmyer S. Pearl
Published: June 2023

This essay explores Leo Bersani’s relationship to deconstruction, arguing that although his thinking about language and signification is indebted to the deconstructive tradition, he ultimately departs from this tradition in his structural understanding of desire qua habit. A close reading of a sentence from Homos forms the refrain for a discussion of the ontology of sexuality, the exclusionary nature of desire, resistances of self and world, and the nature of habit.
Femininity
Authors: Musser Amber Jamilla
Published: June 2023

Written in 1987 in response to the aids emergency unfolding in the United States, Leo Bersani’s “Is the Rectum a Grave?” is often described as an early entry into the strain of queer theory that offers queerness as tarrying in abjection, failure, and antisociality. This essay, however, is much more interested in thinking about the ways Bersani mobilizes connections to femininity in “Is the Rectum a Grave?” As Bersani moves from “women and gay men” to “average, law-abiding family” to “being a woman,” femininity haunts, each of these individual nodes further illuminating an insight about femininity with and without women.
Hand
Authors: Gadberry Andrea
Published: June 2023

This essay remarks how a missing “hand” in Leo Bersani’s The Culture of Redemption illuminates more than a rhetorical strategy; with it, Bersani undermines the problem of “incongruent counterparts” made famous by Kant. While Bersani’s “hand” replies most plainly to the logic of hands in Melanie Klein’s “Early Analysis,” as Bersani reads Proust with Klein, it ultimately offers its most powerful gesture in an antiredemptive comparative literary method in which association, rather than a historical or otherwise redemptive justification, undergirds literary-critical argument. With his severed hand, Bersani also offers an unlikely counterpart to Freud’s uncanny.
Maggie
Authors: Jarcho Julia
Published: June 2023

This brief article considers Leo Bersani’s descriptions of Maggie Verver, a character in Henry James’s novel The Golden Bowl, in relation to some of Bersani’s famous arguments about sexuality. Observing that Bersani’s presentation of Maggie in “The Jamesian Lie” and elsewhere makes her an apt figure not just for sexuality but also for Bersani’s later notion of queer sex as a negation of the social, the article considers both how an ampler consideration of this character might reflect back on Bersani’s use of her to instantiate his claims about desire, and how his account of Maggie might speak to readers torn between competing accounts of queer negativity.
Mobility
Authors: Davis Whitney
Published: June 2023

Mobility is one of Leo Bersani’s hardest-working terms, ubiquitous in his many studies of sexuality, art, and culture. This essay examines the valences of the term with specific reference to Bersani’s application of it in visual analyses, notably in his 1985 book on ancient Assyrian narrative sculptures, The Forms of Violence (with photographs by Ulysse Dutoit).