bluuebunny/crossref_metadata_2025 huggingface dataset:
The search for the principle of justice for infertile couples: characterization of the brazilian population and bioethical discussion
Authors: Oppenheimer Drauzio , Rego Francisca , Nunes Rui
Published: September 2023

Background

Infertility is an increasingly prevalent disease in society and is considered by the World Health Organization to be a public health problem. An important ethical issue arises from the clarification of reproductive rights in a fair and equal way. The objective of this study was to deepen and update the knowledge and discussion about the difficulty of accessing infertility treatments in Brazil.

Methods

A cross-sectional observational study was carried out through the application of an online questionnaire that collected the socioeconomic characteristics of couples and identify how barriers to infertility care affect the most vulnerable populations. We included couples who sought medical assistance to achieve pregnancy at two clinics in the states of São Paulo and Minas Gerais.

Results

A total of 201 questionnaires were analyzed. Most couples self-declared as white and the average age of wives was 36 years and husbands 38 years. 65% (65%) of couples would proceed with the treatment in a different city to which they lived, 37% evaluated as having easy access to a medical specialist only after indication, and more than half of the participating have thought about giving up the treatment due to some difficulty in accessing it. 39% of participants sought more than one medical service to find better reception, 42% of couples sought more than one medical service to define where it would be better financially, and 67.2% referred to the high cost of treatments, that is, financial issues, as a great difficulty in accessing medical services and/or treatment. Although 72.6% of couples considered having a good quality of life, 54.2% admitted that infertility and the search for treatment generated anxiety/stress in the couple’s life.

Conclusion

There is a need for public education on reproductive health and for policymakers to raise awareness of the importance of the difficulty that many couples face in seeking treatment to become pregnant, especially in countries with less financial resources. Indeed, it is commonly accepted that there is a universal human right to access healthcare of appropriate quality as a matter of justice. Discussion of access to reproductive technologies should be considered taking into account the longstanding ethical debate regarding fertility, fecundity, and infertility, as well as reproductive care.
Outlooks on using a mobile health intervention for supportive pain management for children and adolescents with cancer: a qualitative study
Authors: Madi Dina , Abi Abdallah Doumit Myrna , Hallal Mohammad , Moubarak Maya M.
Published: September 2023

Background

Considerable improvements in the prognosis of pediatric cancer patients have been achieved over recent decades due to advances in treatment. Nevertheless, as the most common and distressing health issue for pediatrics with cancer, cancer-related pain is still a significant hurdle that impedes patients’ journey to recovery, compromises their quality of life, and delays the positive outcome and effectiveness of their treatments.

Purpose

Taking into consideration that acceptability studies are imperative for the design, evaluation, and implementation of healthcare interventions, this study aims to explore pediatric oncology patients’ readiness to use a mobile health application that emphasizes social assistance and peer support in addition to conventional pain management methods.

Design and methods

This study followed the Qualitative description approach. Twelve participants were chosen based on purposive sampling and maximum variation sampling. Interviews were analyzed using the conventional content analysis.

Results

Analysis of the interviews revealed four major categories: (A) The need for connectedness; (B) An innovative way to connect yet fearful; (C) A 3D approach; (D) Fears of the unfamiliar.

Conclusions

This study is the first in Lebanon and the region to undertake an initiative towards introducing technology for pain assessment and management of children with cancer through a dedicated digital platform. The study results attested to the acceptability and potential utilization of this platform by children with cancer.

Practice implications

Nurses need to be trained to play an essential role in teaching children with cancer about the significance of social support and assisting them to establish their social support network. Children with cancer are encouraged to voice out their need for help. Our proposed application can create an enabling environment to harness the power of social support and provide children with cancer the opportunity to connect on a deeper level in a supportive and pity-free space.
Encouraging death communication in a death-avoidant society: analysis of interviews with death café organizers
Authors: Ito Kae , Tsuda Shuji , Hagiwara Mayumi , Okamura Tsuyoshi
Published: September 2023

Background

Post-war Japanese tend to avoid discussion of death, resulting in a lack of death communication within clinical settings. However, with the aging of society, the significance of conversations and decisions related to end-of-life issues has grown. In 2007, the government established guidelines for decision-making in end-of-life care. Nonetheless, death communication remains a challenge for healthcare professionals in clinical settings.

In contrast, death cafés have spontaneously emerged within communities as informal gatherings to openly discuss and explore death. Learning from death café organizers may help healthcare professionals encourage death communication in a death-avoidant society.

Therefore, a qualitative study was conducted to describe death cafés by examining the underlying motivation and practices through interviews with death café organizers.

Methods

Individual in-depth interviews were conducted with death café organizers. Two key aspects were explored: 1) the underlying motivations of organizers; and 2) the practices and challenges encountered in running death cafés. The interviews were transcribed verbatim and analyzed using a qualitative descriptive approach. Thematic analysis was used.

Results

The study identified two themes representing the underlying motivation of death café organizers: individually-oriented and community-oriented. These themes exhibited contrasting orientations and were collectively termed “individual-community orientation”.

Regarding the practice of death cafés, the focus was on the “attitude towards having attendees with and without grief in the same session.” Participants’ attitudes towards this aspect fell into two categories with opposing orientations: “purification” and “inclusion.” The “purification-inclusion orientation” was more prevalent among organizers who initiated death cafés due to their personal experiences.

A matrix was created to categorize death cafés based on their underlying motivations (individual vs. community-oriented) and practices (purification vs. inclusion). This classification resulted in quadrant 1 (community-oriented, inclusive) and quadrant 3 (individually-oriented, purification). Notably, death cafés in quadrant 1 were often held in temples.

Conclusions

Japanese death cafés can be classified into two categories: individually and purification-oriented and community and inclusive-oriented categories. Healthcare professionals can learn valuable insights from death café organizers, particularly in promoting death communication. Specifically, temple death cafés, with their inclusive practices and orientation towards community, can be particularly beneficial in fostering inclusivity and community engagement.
Personalised modelling of clinical heterogeneity between medium-chain acyl-CoA dehydrogenase patients
Authors: Odendaal Christoff , Jager Emmalie A. , Martines Anne-Claire M. F. , Vieira-Lara Marcel A. , Huijkman Nicolette C. A. , Kiyuna Ligia A. , Gerding Albert , Wolters Justina C. , Heiner-Fokkema Rebecca , van Eunen Karen , Derks Terry G. J. , Bakker Barbara M.
Published: September 2023

Background

Monogenetic inborn errors of metabolism cause a wide phenotypic heterogeneity that may even differ between family members carrying the same genetic variant. Computational modelling of metabolic networks may identify putative sources of this inter-patient heterogeneity. Here, we mainly focus on medium-chain acyl-CoA dehydrogenase deficiency (MCADD), the most common inborn error of the mitochondrial fatty acid oxidation (mFAO). It is an enigma why some MCADD patients—if untreated—are at risk to develop severe metabolic decompensations, whereas others remain asymptomatic throughout life. We hypothesised that an ability to maintain an increased free mitochondrial CoA (CoASH) and pathway flux might distinguish asymptomatic from symptomatic patients.

Results

We built and experimentally validated, for the first time, a kinetic model of the human liver mFAO. Metabolites were partitioned according to their water solubility between the bulk aqueous matrix and the inner membrane. Enzymes are also either membrane-bound or in the matrix. This metabolite partitioning is a novel model attribute and improved predictions. MCADD substantially reduced pathway flux and CoASH, the latter due to the sequestration of CoA as medium-chain acyl-CoA esters. Analysis of urine from MCADD patients obtained during a metabolic decompensation showed an accumulation of medium- and short-chain acylcarnitines, just like the acyl-CoA pool in the MCADD model. The model suggested some rescues that increased flux and CoASH, notably increasing short-chain acyl-CoA dehydrogenase (SCAD) levels. Proteome analysis of MCADD patient-derived fibroblasts indeed revealed elevated levels of SCAD in a patient with a clinically asymptomatic state. This is a rescue for MCADD that has not been explored before. Personalised models based on these proteomics data confirmed an increased pathway flux and CoASH in the model of an asymptomatic patient compared to those of symptomatic MCADD patients.

Conclusions

We present a detailed, validated kinetic model of mFAO in human liver, with solubility-dependent metabolite partitioning. Personalised modelling of individual patients provides a novel explanation for phenotypic heterogeneity among MCADD patients. Further development of personalised metabolic models is a promising direction to improve individualised risk assessment, management and monitoring for inborn errors of metabolism.
Spatial biology of Ising-like synthetic genetic networks
Authors: Simpson Kevin , L’Homme Alfredo , Keymer Juan , Federici Fernán
Published: September 2023

Background

Understanding how spatial patterns of gene expression emerge from the interaction of individual gene networks is a fundamental challenge in biology. Developing a synthetic experimental system with a common theoretical framework that captures the emergence of short- and long-range spatial correlations (and anti-correlations) from interacting gene networks could serve to uncover generic scaling properties of these ubiquitous phenomena.

Results

Here, we combine synthetic biology, statistical mechanics models, and computational simulations to study the spatial behavior of synthetic gene networks (SGNs) in Escherichia coli quasi-2D colonies growing on hard agar surfaces. Guided by the combined mechanisms of the contact process lattice simulation and two-dimensional Ising model (CPIM), we describe the spatial behavior of bi-stable and chemically coupled SGNs that self-organize into patterns of long-range correlations with power-law scaling or short-range anti-correlations. These patterns, resembling ferromagnetic and anti-ferromagnetic configurations of the Ising model near critical points, maintain their scaling properties upon changes in growth rate and cell shape.

Conclusions

Our findings shed light on the spatial biology of coupled and bistable gene networks in growing cell populations. This emergent spatial behavior could provide insights into the study and engineering of self-organizing gene patterns in eukaryotic tissues and bacterial consortia.
Cuticular competing endogenous RNAs regulate insecticide penetration and resistance in a major agricultural pest
Authors: Meng Li-Wei , Yuan Guo-Rui , Chen Meng-Ling , Zheng Li-Sha , Dou Wei , Peng Yu , Bai Wen-Jie , Li Zhen-Yu , Vontas John , Wang Jin-Jun
Published: September 2023

Background

The continuously developing pesticide resistance is a great threat to agriculture and human health. Understanding the mechanisms of insecticide resistance is a key step in dealing with the phenomenon. Insect cuticle is recently documented to delay xenobiotic penetration which breaks the previous stereotype that cuticle is useless in insecticide resistance, while the underlying mechanism remains scarce.

Results

Here, we find the integument contributes over 40.0% to insecticide resistance via different insecticide delivery strategies in oriental fruit fly. A negative relationship exists between cuticle thickening and insecticide penetration in resistant/susceptible, also in field strains of oriental fruit fly which is a reason for integument-mediated resistance. Our investigations uncover a regulator of insecticide penetration that miR-994 mimic treatment causes cuticle thinning and increases susceptibility to malathion, whereas miR-994 inhibitor results in opposite phenotypes. The target of miR-994 is a most abundant cuticle protein (CPCFC) in resistant/susceptible integument expression profile, which possesses capability of chitin-binding and influences the cuticle thickness-mediated insecticide penetration. Our analyses find an upstream transcriptional regulatory signal of miR-994 cascade, long noncoding RNA (lnc19419), that indirectly upregulates CPCFC in cuticle of the resistant strain by sponging miR-994. Thus, we elucidate the mechanism of cuticular competing endogenous RNAs for regulating insecticide penetration and demonstrate it also exists in field strain of oriental fruit fly.

Conclusions

We unveil a regulatory axis of lnc19419 ~ miR-994 ~ CPCFC on the cuticle thickness that leads to insecticide penetration resistance. These findings indicate that competing endogenous RNAs regulate insecticide resistance by modulating the cuticle thickness and provide insight into the resistance mechanism in insects.
Triangulating evidence from observational and Mendelian randomization studies of ketone bodies for cognitive performance
Authors: Sae-jie Wichanon , Supasai Suangsuda , Kivimaki Mika , Price Jackie F. , Wong Andrew , Kumari Meena , Engmann Jorgen , Shah Tina , Schmidt Amand F. , Gaunt Tom R. , Hingorani Aroon , Charoen Pimphen ,   on behalf of the UCLEB Consortium
Published: September 2023

Background

Ketone bodies (KBs) are an alternative energy supply for brain functions when glucose is limited. The most abundant ketone metabolite, 3-β-hydroxybutyrate (BOHBUT), has been suggested to prevent or delay cognitive impairment, but the evidence remains unclear. We triangulated observational and Mendelian randomization (MR) studies to investigate the association and causation between KBs and cognitive function.

Methods

In observational analyses of 5506 participants aged ≥ 45 years from the Whitehall II study, we used multiple linear regression to investigate the associations between categorized KBs and cognitive function scores. Two-sample MR was carried out using summary statistics from an in-house KBs meta-analysis between the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium and Kettunen et al. (N = 45,031), and publicly available summary statistics of cognitive performance and Alzheimer’s disease (AD) from the Social Science Genetic Association Consortium (N = 257,841), and the International Genomics of Alzheimer’s Project (N = 54,162), respectively. Both strong (P < 5 × 10−8) and suggestive (P < 1 × 10−5) sets of instrumental variables for BOHBUT were applied. Finally, we performed cis-MR on OXCT1, a well-known gene for KB catabolism.

Results

BOHBUT was positively associated with general cognitive function (β = 0.26, P = 9.74 × 10−3). In MR analyses, we observed a protective effect of BOHBUT on cognitive performance (inverse variance weighted: βIVW = 7.89 × 10−2, PIVW = 1.03 × 10−2; weighted median: βW-Median = 8.65 × 10−2, PW-Median = 9.60 × 10−3) and a protective effect on AD (βIVW =  − 0.31, odds ratio: OR = 0.74, PIVW = 3.06 × 10−2). Cis-MR showed little evidence of therapeutic modulation of OXCT1 on cognitive impairment.

Conclusions

Triangulation of evidence suggests that BOHBUT has a beneficial effect on cognitive performance. Our findings raise the hypothesis that increased BOHBUT may improve general cognitive functions, delaying cognitive impairment and reducing the risk of AD.
Evidence of questionable research practices in clinical prediction models
Authors: White Nicole , Parsons Rex , Collins Gary , Barnett Adrian
Published: September 2023

Background

Clinical prediction models are widely used in health and medical research. The area under the receiver operating characteristic curve (AUC) is a frequently used estimate to describe the discriminatory ability of a clinical prediction model. The AUC is often interpreted relative to thresholds, with “good” or “excellent” models defined at 0.7, 0.8 or 0.9. These thresholds may create targets that result in “hacking”, where researchers are motivated to re-analyse their data until they achieve a “good” result.

Methods

We extracted AUC values from PubMed abstracts to look for evidence of hacking. We used histograms of the AUC values in bins of size 0.01 and compared the observed distribution to a smooth distribution from a spline.

Results

The distribution of 306,888 AUC values showed clear excesses above the thresholds of 0.7, 0.8 and 0.9 and shortfalls below the thresholds.

Conclusions

The AUCs for some models are over-inflated, which risks exposing patients to sub-optimal clinical decision-making. Greater modelling transparency is needed, including published protocols, and data and code sharing.
Effect of chimeric antigen receptor T cells against protease-activated receptor 1 for treating pancreatic cancer
Authors: Hung Hao-Chien , Fan Ming-Huei , Wang Daniel , Miao Carol H. , Su Pong , Liu Chao-Lien
Published: September 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a 5-year survival rate of 6% following a diagnosis, and novel therapeutic modalities are needed. Protease-activated receptor 1 (PAR1) is abundantly overexpressed by both tumor cells and multiple stroma cell subsets in the tumor microenvironment (TME), thereby offering a suitable immunotherapy target.

Methods

A chimeric antigen receptor (CAR) strategy was applied to target PAR1 using a human anti-PAR1 scFv antibody fused to the transmembrane region with two co-stimulatory intracellular signaling domains of cluster of differentiation 28 (CD28) and CD137 (4-1BB), added to CD3ζ in tandem.

Results

The engineered PAR1CAR-T cells eliminated PAR1 overexpression and transforming growth factor (TGF)-β-mediated PAR1-upregulated cancer cells by approximately 80% in vitro. The adoptive transfer of PAR1CAR-T cells was persistently enhanced and induced the specific regression of established MIA PaCa-2 cancer cells by > 80% in xenograft models. Accordingly, proinflammatory cytokines/chemokines increased in CAR-T-cell-treated mouse sera, whereas Ki67 expression in tumors decreased. Furthermore, the targeted elimination of PAR1-expressing tumors reduced matrix metalloproteinase 1 (MMP1) levels, suggesting that the blocking of the PAR1/MMP1 pathway constitutes a new therapeutic option for PDAC treatment.

Conclusions

Third-generation PAR1CAR-T cells have antitumor activity in the TME, providing innovative CAR-T-cell immunotherapy against PDAC.
BMI-based obesity classification misses children and adolescents with raised cardiometabolic risk due to increased adiposity
Authors: Zapata J. Karina , Azcona-Sanjulian M. Cristina , Catalán Victoria , Ramírez Beatriz , Silva Camilo , Rodríguez Amaia , Escalada Javier , Frühbeck Gema , Gómez-Ambrosi Javier
Published: September 2023

Objective

To assess how inaccurately the body mass index (BMI) is used to diagnose obesity compared to body fat percentage (BF%) measurement and to compare the cardiometabolic risk in children and adolescents with or without obesity according to BMI but with a similar BF%.

Methods

A retrospective cross-sectional investigation was conducted including 553 (378 females/175 males) white children and adolescents aged 6–17 years, 197 with normal weight (NW), 144 with overweight (OW) and 212 with obesity (OB) according to BMI. In addition to BMI, BF% measured by air displacement plethysmography, as well as markers of cardiometabolic risk had been determined in the existing cohort.

Results

We found that 7% of subjects considered as NW and 62% of children and adolescents classified as OW according to BMI presented a BF% within the obesity range. Children and adolescents without obesity by the BMI criterion but with obesity by BF% exhibited higher blood pressure and C-reactive protein (CRP) in boys, and higher blood pressure, glucose, uric acid, CRP and white blood cells count, as well as reduced HDL-cholesterol, in girls, similar to those with obesity by BMI and BF%. Importantly, both groups of subjects with obesity by BF% showed a similarly altered glucose homeostasis after an OGTT as compared to their NW counterparts.

Conclusions

Results from the present study suggest increased cardiometabolic risk factors in children and adolescents without obesity according to BMI but with obesity based on BF%. Being aware of the difficulty in determining body composition in everyday clinical practice, our data show that its inclusion could yield clinically useful information both for the diagnosis and treatment of overweight and obesity.
Optimization of polyhydroxyalkanoate production in Halomonas sp. YLGW01 using mixed volatile fatty acids: a study on mixture analysis and fed-batch strategy
Authors: Park Yerin , Jeon Jong-Min , Park Jea-Kyung , Yang Yung-Hun , Choi Shin Sik , Yoon Jeong-Jun
Published: September 2023

Polyhydroxyalkanoate (PHA) is one of the most promising materials for replacing petroleum-based plastics, and it can be produced from various renewable biomass sources. In this study, PHA production was conducted using Halomonas sp. YLGW01 utilizing mixed volatile fatty acids (VFAs) as carbon sources. The ratio and concentration of carbon and nitrogen sources were optimized through mixture analysis and organic nitrogen source screening, respectively. It was found that the highest cell dry weight (CDW) of 3.15 g/L and PHA production of 1.63 g/L were achieved when the ratio of acetate to lactate in the mixed VFAs was 0.45:0.55. Furthermore, supplementation of organic nitrogen sources such as soytone resulted in a ninefold increase in CDW (reaching 2.32 g/L) and a 22-fold increase in PHA production (reaching 1.60 g/L) compared to using inorganic nitrogen sources. Subsequently, DO-stat, VFAs consumption rate stat, and pH–stat fed-batch methods were applied to investigate and evaluate PHA productivity. The results showed that when pH–stat-based VFAs feeding was employed, a CDW of 7 g/L and PHA production of 5.1 g/L were achieved within 68 h, with a PHA content of 73%. Overall, the pH–stat fed-batch strategy proved to be effective in enhancing PHA production by Halomonas sp. YLGW01 utilizing VFAs.
Description of the design of a mixed-methods study to assess the burden and determinants of malaria transmission for tailoring of interventions (microstratification) in Ibadan and Kano metropolis
Authors: Ozodiegwu Ifeoma D. , Ogunwale Akintayo O. , Surakat Olabanji , Akinyemi Joshua O. , Bamgboye Eniola A. , Fagbamigbe Adeniyi F. , Bello Musa Muhammad , Adamu Al-Mukhtar Y. , Uhomobhi Perpetua , Ademu Cyril , Okoronkwo Chukwu , Adeleke Monsuru , Ajayi IkeOluwapo O.
Published: September 2023

Background

Rapid urbanization in Nigerian cities may lead to localized variations in malaria transmission, particularly with a higher burden in informal settlements and slums. However, there is a lack of available data to quantify the variations in transmission risk at the city level and inform the selection of appropriate interventions. To bridge this gap, field studies will be undertaken in Ibadan and Kano, two major Nigerian cities. These studies will involve a blend of cross-sectional and longitudinal epidemiological research, coupled with longitudinal entomological studies. The primary objective is to gain insights into the variation of malaria risk at the smallest administrative units, known as wards, within these cities.

Methods/results

The findings will contribute to the tailoring of interventions as part of Nigeria’s National Malaria Strategic Plan. The study design incorporates a combination of model-based clustering and on-site visits for ground-truthing, enabling the identification of environmental archetypes at the ward-level to establish the study’s framework. Furthermore, community participatory approaches will be utilized to refine study instruments and sampling strategies. The data gathered through cross-sectional and longitudinal studies will contribute to an enhanced understanding of malaria risk in the metropolises of Kano and Ibadan.

Conclusions

This paper outlines pioneering field study methods aimed at collecting data to inform the tailoring of malaria interventions in urban settings. The integration of multiple study types will provide valuable data for mapping malaria risk and comprehending the underlying determinants. Given the importance of location-specific data for microstratification, this study presents a systematic process and provides adaptable tools that can be employed in cities with limited data availability.
Identification of multidrug chemoresistant genes in head and neck squamous cell carcinoma cells
Authors: Khera Neha , Rajkumar Asvika Soodhalaagunta , Abdulkader M Alkurdi Khlood , Liu Zhiao , Ma Hong , Waseem Ahmad , Teh Muy-Teck
Published: September 2023

Multidrug resistance renders treatment failure in a large proportion of head and neck squamous cell carcinoma (HNSCC) patients that require multimodal therapy involving chemotherapy in conjunction with surgery and/or radiotherapy. Molecular events conferring chemoresistance remain unclear. Through transcriptome datamining, 28 genes were subjected to pharmacological and siRNA rescue functional assays on 12 strains of chemoresistant cell lines each against cisplatin, 5-fluorouracil (5FU), paclitaxel (PTX) and docetaxel (DTX). Ten multidrug chemoresistance genes (TOP2A, DNMT1, INHBA, CXCL8, NEK2, FOXO6, VIM, FOXM1B, NR3C1 and BIRC5) were identified. Of these, four genes (TOP2A, DNMT1, INHBA and NEK2) were upregulated in an HNSCC patient cohort (n = 221). Silencing NEK2 abrogated chemoresistance in all drug-resistant cell strains. INHBA and TOP2A were found to confer chemoresistance in majority of the drug-resistant cell strains whereas DNMT1 showed heterogeneous results. Pan-cancer Kaplan-Meier survival analysis on 21 human cancer types revealed significant prognostic values for INHBA and NEK2 in at least 16 cancer types. Drug library screens identified two compounds (Sirodesmin A and Carfilzomib) targeting both INHBA and NEK2 and re-sensitised cisplatin-resistant cells. We have provided the first evidence for NEK2 and INHBA in conferring chemoresistance in HNSCC cells and siRNA gene silencing of either gene abrogated multidrug chemoresistance. The two existing compounds could be repurposed to counteract cisplatin chemoresistance in HNSCC. This finding may lead to novel personalised biomarker-linked therapeutics that can prevent and/or abrogate chemoresistance in HNSCC and other tumour types with elevated NEK2 and INHBA expression. Further investigation is necessary to delineate their signalling mechanisms in tumour chemoresistance.
Selenium-integrated conjugated oligomer nanoparticles with high photothermal conversion efficiency for NIR-II imaging-guided cancer phototheranostics in vivo
Authors: Yang Lele , Gao Yijian , Wei Jinchao , Cheng Zehua , Wu Sijia , Zou Liang , Li Shengliang , Li Peng
Published: September 2023

Second near-infrared (NIR-II) fluorescence imaging in the range of 1000–1700 nm has great prospects for in vivo imaging and theranostics monitoring. At present, few NIR-II probes with theranostics properties have been developed, especially the high-performance organic theranostics material remains underexploited. Herein, we demonstrate a selenium (Se)-tailoring method to develop high-efficient NIR-II imaging-guided material for in vivo cancer phototheranostics. Via Se-tailoring strategy, conjugated oligomer TPSe-based nanoparticles (TPSe NPs) achieve bright NIR-II emission up to 1400 nm and exhibit a relatively high photothermal conversion efficiency of 60% with good stability. Moreover, the TPSe NPs demonstrate their photothermal ablation of cancer cells in vitro and tumor in vivo with the guidance of NIR-II imaging. It is worth noting that the TPSe NPs have good biocompatibility without obvious side effects. Thus, this work provides new insight into the development of NIR-II theranostics agents.
Loss of ACTL7A causes small head sperm by defective acrosome-acroplaxome-manchette complex
Authors: Zhang Yini , Tang Jianan , Wang Xuemei , Sun Yisi , Yang Tianying , Shen Xiaorong , Yang Xinyue , Shi Huijuan , Sun Xiaoxi , Xin Aijie
Published: September 2023

Background

Actin-like 7 A (ACTL7A) is essential for acrosome formation, fertilization and early embryo development. ACTL7A variants cause acrosome detachment responsible for male infertility and early embryonic arrest. In this study, we aim to explore the additional functions of ACTL7A beyond the process of acrosome biogenesis and investigate the possible underlying mechanisms.

Methods

Nuclear morphology analysis was used to observe the sperm head shape of ACTL7A-mutated patients. Actl7a knock-out (KO) mouse model was generated. Immunofluorescence and transmission electron microscopy (TEM) were performed to analyze the structure of spermatids during spermiogenesis. Tandem mass tags labeling quantitative proteomics strategy was employed to explore the underlying molecular mechanisms. The expression levels of key proteins in the pathway were analyzed by western blotting. Intracytoplasmic sperm injection (ICSI)-artificial oocyte activation (AOA) technology was utilized to overcome fertilization failure in male mice with a complete knockout of Actl7a.

Results

The new phenotype of small head sperm associated with loss of ACTL7A in patients was discovered, and further confirmed in Actl7a-KO mice. Immunofluorescence and TEM analyses revealed that the deletion of ACTL7A damaged the formation of acrosome-acroplaxome-manchette complex, leading to abnormalities in the shaping of sperm heads. Moreover, a proteomic analysis of testes from WT and Actl7a-KO mice revealed that differentially expressed genes were notably enriched in PI3K/AKT/mTOR signaling pathway which is strongly associated with autophagy. Inhibition of autophagy via PI3K/AKT/mTOR signaling pathway activation leading to PDLIM1 accumulation might elucidate the hindered development of manchette in Actl7a-KO mice. Remarkably, AOA successfully overcame fertilization failure and allowed for the successful production of healthy offspring from the Actl7a complete knockout male mice.

Conclusions

Loss of ACTL7A causes small head sperm as a result of defective acrosome-acroplaxome-manchette complex via autophagy inhibition. ICSI-AOA is an effective technique to rescue male infertility resulting from ACTL7A deletion. These findings provide essential evidence for the diagnosis and treatment of patients suffering from infertility.
Regulation of anoikis by extrinsic death receptor pathways
Authors: Han Ying-Hao , Wang Yuan , Lee Seung-Jae , Jin Mei-Hua , Sun Hu-Nan , Kwon Taeho
Published: September 2023

Metastatic cancer cells can develop anoikis resistance in the absence of substrate attachment and survive to fight tumors. Anoikis is mediated by endogenous mitochondria-dependent and exogenous death receptor pathways, and studies have shown that caspase-8-dependent external pathways appear to be more important than the activity of the intrinsic pathways. This paper reviews the regulation of anoikis by external pathways mediated by death receptors. Different death receptors bind to different ligands to activate downstream caspases. The possible mechanisms of Fas-associated death domain (FADD) recruitment by Fas and TNF receptor 1 associated-death domain (TRADD) recruitment by tumor necrosis factor receptor 1 (TNFR1), and DR4- and DR5-associated FADD to induce downstream caspase activation and regulate anoikis were reviewed. This review highlights the possible mechanism of the death receptor pathway mediation of anoikis and provides new insights and research directions for studying tumor metastasis mechanisms.
STING signaling activation modulates macrophage polarization via CCL2 in radiation-induced lung injury
Authors: Ni Jianjiao , Guo Tiantian , Zhou Yue , Jiang Shanshan , Zhang Long , Zhu Zhengfei
Published: September 2023

Background

Radiation-induced lung injury (RILI) is a prevalent complication of thoracic radiotherapy in cancer patients. A comprehensive understanding of the underlying mechanisms of RILI is essential for the development of effective prevention and treatment strategies.

Methods

To investigate RILI, we utilized a mouse model that received 12.5 Gy whole-thoracic irradiation. The evaluation of RILI was performed using a combination of quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), histology, western blot, immunohistochemistry, RNA sequencing, and flow cytometry. Additionally, we established a co-culture system consisting of macrophages, lung epithelial cells, and fibroblasts for in vitro studies. In this system, lung epithelial cells were irradiated with a dose of 4 Gy, and we employed STING knockout macrophages. Translational examinations were conducted to explore the relationship between STING expression in pre-radiotherapy lung tissues, dynamic changes in circulating CCL2, and the development of RILI.

Results

Our findings revealed significant activation of the cGAS-STING pathway and M1 polarization of macrophages in the lungs of irradiated mice. In vitro studies demonstrated that the deficiency of cGAS-STING signaling led to impaired macrophage polarization and RILI. Through RNA sequencing, cytokine profiling, and rescue experiments using a CCL2 inhibitor called Bindarit, we identified the involvement of CCL2 in the regulation of macrophage polarization and the development of RILI. Moreover, translational investigations using patient samples collected before and after thoracic radiotherapy provided additional evidence supporting the association between cGAS-STING signaling activity, CCL2 upregulation, and the development of radiation pneumonitis.

Conclusions

The cGAS-STING signaling pathway plays a crucial role in regulating the recruitment and polarization of macrophages, partly through CCL2, during the pathogenesis of RILI.
Suboptimal birth spacing practice and its predictors among reproductive-age women in Sub-Saharan African countries: a multilevel mixed-effects modeling with robust Poisson regression
Authors: Mare Kusse Urmale , Sabo Kebede Gemeda , Mohammed Ahmed Adem , Leyto Simeon Meskele , Mulaw Getahun Fentaw , Tebeje Tsion Mulat , Aychiluhm Setognal Birara , Ebrahim Oumer Abdulkadir , Wuneh Abel Gebre , Seifu Beminate Lemma
Published: September 2023

Background

Despite the availability of exempted family planning services, a significant proportion of women in African countries continue to experience inadequately spaced pregnancies. To the authors’ knowledge, evidence of suboptimal birth intervals at the SSA level is lacking and previous studies have been limited to specific geographic area. Therefore, this analysis was aimed to estimate the pooled prevalence of suboptimal birth spacing and its predictors among childbearing women in SSA.

Methods

Pooled DHS data from 35 SSA countries were used and a weighted sample of 221,098 reproductive-age women was considered in the analysis. The survey across all countries employed a cross-sectional study design and collected data on basic sociodemographic characteristics and different health indicators. Forest plot was used to present the overall and country-level prevalence of suboptimal birth spacing. Multilevel mixed-effects models with robust Poisson regression were fitted to identify the predictors of suboptimal birth spacing. Akaike’s and Bayesian information criteria and deviance were used to compare the models. In a multivariable regression model, a p-value less than 0.05 and an adjusted prevalence ratio with the corresponding 95% CI were used to assess the statistical significance of the explanatory variables.

Results

The pooled prevalence of suboptimal birth spacing among women in SSA was 43.91% (43.71%-44.11%), with South Africa having the lowest prevalence (23.25%) and Chad having the highest (59.28%). It was also found that 14 of the 35 countries had a prevalence above the average for SSA. Rural residence [APR (95% CI) = 1.10 (1.12–1.15)], non-exposure to media [APR (95% CI) = 1.08 (1.07–1.11)], younger maternal age [APR (95% CI) = 2.05 (2.01–2.09)], non-use of contraception [APR (95% CI) = 1.18 (1.16–1.20)], unmet need for family planning [APR (95% CI) = 1.04 (1.03–1.06)], higher birth order [APR (95% CI) = 1.31 (1.28–1.34)], and desire to have at least six children [APR (95% CI) = 1.14 (1.13–1.16)] were the predictors of suboptimal birth spacing practice.

Conclusion

More than four out of ten reproductive-age women in SSA countries gave birth to a subsequent child earlier than the recommended birth spacing, with considerable variations across the countries. Thus, interventions designed at enhancing optimal birth spacing should pay particular attention to young and socioeconomically disadvantaged women and those residing in rural regions. Strengthening community health programs and improving accessibility and availabilities of fertility control methods that ultimately impacts optimal reproductive behaviors is crucial to address contraceptive utilization and unmet need.
Establishment of an NPK nutrient monitor system in yield-graded cotton petioles under drip irrigation
Authors: Dong Zhiqiang , Liu Yang , Li Minghua , Ci Baoxia , Feng Xiaokang , Wen Shuai , Lu Xi , He Zheng , Ma Fuyu
Published: September 2023

Background

The determination of nutrient content in the petiole is one of the important methods for achieving cotton fertilization management. The establishment of a monitoring system for the nutrient content of cotton petioles during important growth periods under drip irrigation is of great significance for achieving precise fertilization and environmental protection.

Methods

A total of 100 cotton fields with an annual yield of 4500–7500 kg/ha were selected among the main cotton-growing areas of Northern Xinjiang. The nitrate nitrogen (NO3−–N), inorganic phosphorus (PO43−–P) and inorganic potassium (K+–K) content and yield of cotton petioles were recorded. Based on a yield of 6000 kg/ha as the dividing line, a two-level and yield-graded monitoring system for NO3−–N, PO43−–P and K+–K in cotton petioles during important growth periods was established, and predictive yield models for NO3−–N, PO43−–P and K+–K in petioles during important growth periods were established.

Results

The results showed found that the yields of the 100 cotton fields surveyed were normally distributed. Therefore, two yield grades were classified using 6000 kg/ha as a criterion. Under different yield-graded, the NO3−–N, PO43−–P and K+–K content of petiole at important growth stages was significantly positively correlated with yield. Further, the variation range of NO3−–N, PO43−–P and K+–K content in petioles could be used as a standard for yield-graded. In addition, a yield prediction model for the NO3−–N, PO43−–P and K+–K content of petioles was developed. The SSO-BP validation model performed the best (R2 = 0.96, RMSE = 0.06 t/ha, MAE = 0.05 t/ha) in the full bud stage, which was 12.9% higher than the BP validation model. However, the RMSE and MAE were decreased by 86.7% and 88.1%, respectively.

Conclusion

The establishment of NPK nutrition monitor system of cotton petioles under drip irrigation based on yield-graded provides an important basis for nutrition monitor of cotton petiole under drip irrigation in Xinjiang. It also provides a new method for cotton yield prediction.
Transcriptome-wide association study identifies new susceptibility genes and pathways for spondyloarthritis
Authors: Su Xiaochen , Chen Anfa , Teng Menghao , Ji Wenchen , Zhang Yingang
Published: September 2023

Background

Spondyloarthritis (SpA) is a group of multifactorial bone diseases influenced by genetic factors, the environment and lifestyle. However, current studies have found a limited number of SpA-related genes, and the genetic and pathogenic mechanisms of SpA are still unclear.

Methods

A tissue-specific transcriptome-wide association study (TWAS) of SpA was performed using GWAS (including 3966 SpA patients and 448,298 controls) summary data and gene expression weights of whole blood and skeletal muscle. The SpA-associated genes identified by TWAS were further compared with the differentially expressed genes (DEGs) identified in the SpA gene expression profile acquired from the Gene Expression Omnibus database (GEO, GSE58667). Finally, functional enrichment and annotation analyses of the identified genes were performed.

Results

The TWAS detected 499 suggestive genes associated with SpA in whole blood and skeletal muscle, such as CTNNAL1 (PSM = 3.04 × 10−2, PWB = 9.58 × 10−3). The gene expression profile of SpA identified 20 candidate genes that overlapped in the TWAS data, such as MCM4 (PTWAS = 1.32 × 10−2, PDEG = 2.75 × 10−2) and KIAA1109 (PTWAS = 3.71 × 10−2, PDEG = 4.67 × 10−2). Enrichment analysis of the genes identified by TWAS identified 93 significant GO terms and 33 KEGG pathways, such as mitochondrion organization (GO: 0007005) and axon guidance (hsa04360).

Conclusion

We identified multiple candidate genes that were genetically related to SpA. Our study may provide novel clues regarding the genetic mechanism, diagnosis, and treatment of SpA.
Double posteromedial portals versus single posteromedial portal for arthroscopic management of popliteal cysts
Authors: Ma Rui , Zhu Zheyue , Liu Dan , Wang Kunzheng , Yang Pei
Published: September 2023

Background

As a common disease in orthopedic clinics, popliteal cysts often coexist with intra-articular lesions. Compared with traditional open surgery, arthroscopic treatment of popliteal cysts is less traumatic, and intra-articular lesions can be treated. The ‘one-way valve’ mechanism of the popliteal cyst can be removed by expanding the communication between the articular cavity and the cyst to avoid cyst recurrence. In terms of arthroscopic techniques, the comparison of clinical effects between the double posteromedial portal (DPP) and single posteromedial portal (SPP) has rarely been studied. The purpose of this retrospective study was to compare the clinical effects of DPP and SPP.

Methods

A total of 46 consecutive patients with symptomatic popliteal cysts who underwent arthroscopic treatment were included in this study and followed for approximately 1 year. All patients were divided into two groups according to the arthroscopic portals (DPP group and SPP group). The cyst size, Lysholm score and Rauschening–Lindgren (R–L) grade were evaluated before the operation for all patients, and the intra-articular lesions, operative time and complications were recorded after operation. At the last follow-up, the Lysholm score and R–L grade were recorded, and magnetic resonance imaging was used to evaluate the outcome of the cyst. The clinical data of the two groups was statistically compared and analyzed.

Results

There were no significant differences in preoperative cyst size, Lysholm score or R–L grade between the two groups (P > 0.05). The operation time of the DPP group (67.52 ± 18.23 min) was longer than that of the SPP group (55.95 ± 16.40 min) (P = 0.030), but the recurrence rate of cysts in the DPP group (0%) was obviously lower than that in the SPP group (19.0%) (P = 0.046). There were no significant differences in the Lysholm score, R–L grade or complication rate between the two groups at the last follow-up (P > 0.05).

Conclusion

Arthroscopic treatment of popliteal cysts using double posteromedial portals was a safe and effective surgical method.

Trial registration: ChiCTR, ChiCTR2200060115. Registered 19 May 2022, https://www.chictr.org.cn/showproj.html?proj=133199
ORPHAcodes use for the coding of rare diseases: comparison of the accuracy and cross country comparability
Authors: Mazzucato Monica , Pozza Laura Visonà Dalla , Facchin Paola , Angin Cèline , Agius Francis , Cavero-Carbonell Clara , Corrochano Virginia , Hanusova Katerina , Kirch Kurt , Lambert Deborah , Lucano Caterina , Maiella Sylvie , Panzaru Monica , Rusu Cristina , Weber Stefanie , Zurriaga Oscar , Zvolsky Miroslav , Rath Ana
Published: September 2023

Background

Estimates of rare disease (RD) population impact in terms of number of affected patients and accurate disease definition is hampered by their under-representation in current coding systems. This study tested the use of a specific RD codification system (ORPHAcodes) in five European countries/regions (Czech Republic, Malta, Romania, Spain, Veneto region-Italy) across different data sources over the period January 2019-September 2021.

Results

Overall, 3133 ORPHAcodes were used to describe RD diagnoses, mainly corresponding to the disease/subtype of disease aggregation level of the Orphanet classification (82.2%). More than half of the ORPHAcodes (53.6%) described diseases having a very low prevalence (< 1 case per million), and most commonly captured rare developmental defects during embryogenesis (31.3%) and rare neurological diseases (17.6%). ORPHAcodes described disease entities more precisely than corresponding ICD-10 codes in 83.4% of cases.

Conclusions

ORPHAcodes were found to be a versatile resource for the coding of RD, able to assure easiness of use and inter-country comparability across population and hospital databases. Future research on the impact of ORPHAcoding as to the impact of numbers of RD patients with improved coding in health information systems is needed to inform on the real magnitude of this public health issue.