bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping pedestrian network level outdoor heat hazard distributions in Philadelphia
Authors: Li Xiaojiang
Published: August 2024

With the rise of global temperature, many cities are suffering from more and more frequent extreme heat in hot summers. Quantitative information on the spatial distributions of urban heat has become more and more important for extreme heat mitigation and adaptation in cities. This study first investigated the fine-level heat hazard distributions at the sidewalk and building block level from the pedestrian perspective in Philadelphia, Pennsylvania. The urban microclimate modeling based on a high-resolution urban geometrical model was used to generate the 1m resolution outdoor heat hazard map in the study area. The sidewalk map was overlaid on the generated high-resolution heat hazard map to estimate the sidewalk level heat hazard. Based on the sidewalk level heat hazard map, this study further calculated the heat hazard level in the 400m walkshed along sidewalks for each building block. The building level hazard data were then aggregated at the census tract level to compare with the socioeconomic and racial/ethnic variables. The result shows that neighborhoods with higher proportion of African Americans have a higher heat hazard level in Philadelphia. This study would provide new insights for developing more thermally comfortable and pedestrian-friendly neighborhoods in the context of climate change.
Looking Forward: Music, Disability, and Inclusion
Authors: Draper Ellary A.
Published: August 2024

The ways in which we think about and refer to people with disabilities has changed considerably over the years; the terminology and educational strategies used continue to evolve. It is important for music teachers to stay well-informed on the latest research, labels being used, and best practice, especially when working with students with disabilities in inclusive music classrooms. This article provides guidance for music educators on staying well-informed, along with recommendations for researchers concerning students with disabilities.
The Importance of Playful General Music in High School
Authors: Varner Edward
Published: August 2024

Play-based learning is a well-supported strategy in early childhood and elementary education. However, new research also suggests that teenagers learn well from playing, too. As some attempt to shift toward more learner-centered models, music teachers may find that they need to help students reconnect with the joy and play inherent in authentic learning. This column advocates four strategies to help reinvigorate the high school music class and turn it into an oasis of learning or a much-needed sanctuary in the middle of a student’s day. The strategies for using play-based learning with older students can get them more engaged with course content, make natural social emotional learning alignments, create opportunities for students to think differently, and enhance creativity and the desire to learn.
An unbiased lncRNA dropout CRISPR-Cas9 screen reveals RP11-350G8.5 as a novel therapeutic target for multiple myeloma
Authors: Grillone Katia , Ascrizzi Serena , Cremaschi Paolo , Amato Jussara , Polerà Nicoletta , Croci Ottavio , Rocca Roberta , Riillo Caterina , Conforti Francesco , Graziano Raffaele , Brancaccio Diego , Caracciolo Daniele , Alcaro Stefano , Pagano Bruno , Randazzo Antonio , Tagliaferri Pierosandro , Iorio Francesco , Tassone Pierfrancesco
Published: August 2024

Multiple myeloma (MM) is an incurable malignancy characterized by altered expression of coding and noncoding genes promoting tumor growth and drug resistance. Although the crucial role of long noncoding RNAs (lncRNAs) in MM is clearly established, the function of the noncoding RNAome, which might allow the design of novel therapeutics, is largely unknown. We performed an unbiased CRISPR-Cas9 loss-of-function screen of 671 lncRNAs in MM cells and their bortezomib (BZB)–resistant derivative. To rank functionally and clinically relevant candidates, we designed and used a bioinformatic prioritization pipeline combining functional data from cellular screens with prognostic and transcriptional data from patients with MM. With this approach, we unveiled and prioritized 8 onco-lncRNAs essential for MM cell fitness, associated with high expression and poor prognosis in patients with MM. The previously uncharacterized RP11-350G8.5 emerged as the most promising target, irrespective of BZB resistance. We (1) demonstrated the anti-tumoral effect obtained by RP11-350G8.5 inhibition in vitro and in vivo; (2) highlighted a modulation of the unfolded protein response and the induction of immunogenic cell death triggered by the RP11-350G8.5 knockout, via RNA sequencing and molecular studies; (3) characterized its cytoplasmic homing through RNA fluorescence in situ hybridization; and (4) predicted its 2-dimensional structure and identified 2 G-quadruplex and 3 hairpin-forming regions by biophysical assays, including thioflavin T, 1H nuclear magnetic resonance, and circular dichroism, to pave the way to the development of novel targeted therapeutics. Overall, we provided innovative insights about unexplored lncRNAs in MM and identified RP11-350G8.5 as an oncogenic target for treatment-naïve and BZB-resistant patients with MM.
Coagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivo
Authors: Puy Cristina , Moellmer Samantha A. , Pang Jiaqing , Vu Helen H. , Melrose Alexander R. , Lorentz Christina U. , Tucker Erik I. , Shatzel Joseph J. , Keshari Ravi S. , Lupu Florea , Gailani David , McCarty Owen J. T.
Published: August 2024

Loss of endothelial barrier function contributes to the pathophysiology of many inflammatory diseases. Coagulation factor XI (FXI) plays a regulatory role in inflammation. Although activation of FXI increases vascular permeability in vivo, the mechanism by which FXI or its activated form FXIa disrupts endothelial barrier function is unknown. We investigated the role of FXIa in human umbilical vein endothelial cell (HUVEC) or human aortic endothelial cell (HAEC) permeability. The expression patterns of vascular endothelial (VE)-cadherin and other proteins of interest were examined by western blot or immunofluorescence. Endothelial cell permeability was analyzed by Transwell assay. We demonstrate that FXIa increases endothelial cell permeability by inducing cleavage of the VE-cadherin extracellular domain, releasing a soluble fragment. The activation of a disintegrin and metalloproteinase 10 (ADAM10) mediates the FXIa-dependent cleavage of VE-cadherin, because adding an ADAM10 inhibitor prevented the cleavage of VE-cadherin induced by FXIa. The binding of FXIa with plasminogen activator inhibitor 1 and very low–density lipoprotein receptor on HUVEC or HAEC surfaces activates vascular endothelial growth receptor factor 2 (VEGFR2). The activation of VEGFR2 triggers the mitogen-activated protein kinase (MAPK) signaling pathway and promotes the expression of active ADAM10 on the cell surface. In a pilot experiment using an established baboon model of sepsis, the inhibition of FXI activation significantly decreased the levels of soluble VE-cadherin to preserve barrier function. This study reveals a novel pathway by which FXIa regulates vascular permeability. The effect of FXIa on barrier function may be another way by which FXIa contributes to the development of inflammatory diseases.
Epigenetic regulation of noncanonical menin targets modulates menin inhibitor response in acute myeloid leukemia
Authors: Zhou Xinyue , Zhang Lixia , Aryal Sajesan , Veasey Virginia , Tajik Amanda , Restelli Cecilia , Moreira Steven , Zhang Pengcheng , Zhang Yanfeng , Hope Kristin J. , Zhou Yang , Cheng Changde , Bhatia Ravi , Lu Rui
Published: August 2024

Menin inhibitors that disrupt the menin-MLL interaction hold promise for treating specific acute myeloid leukemia (AML) subtypes, including those with KMT2A rearrangements (KMT2A-r), yet resistance remains a challenge. Here, through systematic chromatin-focused CRISPR screens, along with genetic, epigenetic, and pharmacologic studies in a variety of human and mouse KMT2A-r AML models, we uncovered a potential resistance mechanism independent of canonical menin-MLL targets. We show that a group of noncanonical menin targets, which are bivalently cooccupied by active menin and repressive H2AK119ub marks, are typically downregulated after menin inhibition. Loss of polycomb repressive complex 1.1 (PRC1.1) subunits, such as polycomb group ring finger 1 (PCGF1) or BCL6 corepressor (BCOR), leads to menin inhibitor resistance by epigenetic reactivation of these noncanonical targets, including MYC. Genetic and pharmacological inhibition of MYC can resensitize PRC1.1-deficient leukemia cells to menin inhibition. Moreover, we demonstrate that leukemia cells with the loss of PRC1.1 subunits exhibit reduced monocytic gene signatures and are susceptible to BCL2 inhibition, and that combinational treatment with venetoclax overcomes the resistance to menin inhibition in PRC1.1-deficient leukemia cells. These findings highlight the important roles of PRC1.1 and its regulated noncanonical menin targets in modulating the menin inhibitor response and provide potential strategies to treat leukemia with compromised PRC1.1 function.
Targeting CDC42 reduces skeletal degeneration after hematopoietic stem cell transplantation
Authors: Landspersky Theresa , Stein Merle , Saçma Mehmet , Geuder Johanna , Braitsch Krischan , Rivière Jennifer , Hettler Franziska , Romero Marquez Sandra , Vilne Baiba , Hameister Erik , Richter Daniel , Schönhals Emely , Tuckermann Jan , Verbeek Mareike , Herhaus Peter , Hecker Judith S. , Bassermann Florian , Götze Katharina S. , Enard Wolfgang , Geiger Hartmut , Oostendorp Robert A. J. , Schreck Christina
Published: August 2024

Osteopenia and osteoporosis are common long-term complications of the cytotoxic conditioning regimen for hematopoietic stem cell transplantation (HSCT). We examined mesenchymal stem and progenitor cells (MSPCs), which include skeletal progenitors, from mice undergoing HSCT. Such MSPCs showed reduced fibroblastic colony-forming units frequency, increased DNA damage, and enhanced occurrence of cellular senescence, whereas there was a reduced bone volume in animals that underwent HSCT. This reduced MSPC function correlated with elevated activation of the small Rho guanosine triphosphate hydrolase CDC42, disorganized F-actin distribution, mitochondrial abnormalities, and impaired mitophagy in MSPCs. Changes and defects similar to those in mice were also observed in MSPCs from humans undergoing HSCT. A pharmacological treatment that attenuated the elevated activation of CDC42 restored F-actin fiber alignment, mitochondrial function, and mitophagy in MSPCs in vitro. Finally, targeting CDC42 activity in vivo in animals undergoing transplants improved MSPC quality to increase both bone volume and trabecular bone thickness. Our study shows that attenuation of CDC42 activity is sufficient to attenuate reduced function of MSPCs in a BM transplant setting.
Discontinuing hormonal gender reassignment: a nationwide register study
Authors: Kaltiala Riittakerttu , Helminen Mika , Holttinen Timo , Tuisku Katinka
Published: August 2024

Background

With increasing numbers of people seeking medical gender reassignment, the scientific community has become increasingly aware of the issue of detransitioning from social, hormonal or even surgical gender reassignment (GR). This study aimed to assess the proportion of patients who discontinued their established hormonal gender transition and the risk factors for discontinuation.

Methods

A nationwide register-based follow-up was conducted. Data were analysed via cross-tabulations with chi-square statistics and t tests/ANOVAs. Multivariate analyses were performed via Cox regression, which accounts for differences in follow-up times.

Results

Of the 1,359 subjects who had undergone hormonal GR in Finland from 1996 to 2019, 7.9% discontinued their established hormonal treatment during an average follow-up of 8.5 years. The risk for discontinuing hormonal GR was greater among later cohorts. The hazard ratio was 2.7 (95% confidence interval 1.1–6.1) among those who had accessed gender identity services from 2013 to 2019 compared with those who had come to contact from 1996 to 2005. Discontinuing also appeared to be emerging earlier among those who had entered the process in later years.

Conclusions

The risk of discontinuing established medical GR has increased alongside the increase in the number of patients seeking and proceeding to medical GR. The threshold to initiate medical GR may have lowered, resulting in a greater risk of unbalanced treatment decisions.

Trial registration number (TRN)

Not applicable (the paper does not present a clinical trial).
Exploration of causal relationship between shoulder impingement syndrome and rotator cuff injury: a bidirectional mendelian randomization
Authors: Liu Li , Yang Fan , Liao Ying , Deng Hui , Le Dongsheng , Zhang Chao , Zhao Mailin , Liao Pingsheng , Liang Yingping
Published: August 2024

Backgroup

The pathogenesis of shoulder impingement syndrome (SIS) is still unclear, and its questionable causal relationship with rotator cuff (RC) injury has led to confusion in treatment. The purpose of this study was to explore the bidirectional causal relationship between SIS and RC injury.

Methods

SIS and RC injury datasets downloaded from the IEU Open GWAS project and GWAS catalog databases. Inverse variance weighted (IVW), MR Egger, Weighted median, and Weighted mode were used in this Mendelian randomization (MR) analysis. Cochran’s Q test, leave-one-out, and funnel plot method were used to evaluate heterogeneity between single nucleotide polymorphisms (SNPs). MR-Egger regression was used to test the horizontal pleiotropy of this study.

Results

The IVW method (OR = 1.189, P = 0.0059) suggest the putative causal effect of RC injury on SIS. The results of MR Egger method (OR = 1.236, P = 0.2013), weighted median method (OR = 1.097, P = 0.2428) and weighted mode method (OR = 1.013, P = 0.930) showed no statistically significant (OR = 1.069071, P = 0.6173). Heterogeneity test and horizontal pleiotropy analysis suggested that there was no significant heterogeneity and horizontal pleiotropy in the results of this MR analysis. The reverse MR analysis showed heterogeneity, and the conclusion needs to be further explored.

Conclusions

The results of MR analysis support that RC injury may be causally associated with SIS.
Financial hardship after COVID-19 infection among US Veterans: a national prospective cohort study
Authors: Govier Diana J. , Bui David P. , Hauschildt Katrina E. , Eaton Tammy L. , McCready Holly , Smith Valerie A. , Osborne Thomas F. , Bowling C. Barrett , Boyko Edward J. , Ioannou George N. , Maciejewski Matthew L. , O’Hare Ann M. , Viglianti Elizabeth M. , Bohnert Amy S. B. , Hynes Denise M. , Iwashyna Theodore J.
Published: August 2024

Background

Research suggests an association between COVID-19 infection and certain financial hardships in the shorter term and among single-state and privately insured samples. Whether COVID-19 is associated with financial hardship in the longer-term or among socially vulnerable populations is unknown. Therefore, we examined whether COVID-19 was associated with a range of financial hardships 18 months after initial infection among a national cohort of Veterans enrolled in the Veterans Health Administration (VHA)—the largest national integrated health system in the US. We additionally explored the association between Veteran characteristics and financial hardship during the pandemic, irrespective of COVID-19.

Methods

We conducted a prospective, telephone-based survey. Out of 600 Veterans with COVID-19 from October 2020 through April 2021 who were invited to participate, 194 Veterans with COVID-19 and 194 matched comparators without a history of infection participated. Financial hardship outcomes included overall health-related financial strain, two behavioral financial hardships (e.g., taking less medication than prescribed due to cost), and seven material financial hardships (e.g., using up most or all savings). Weighted generalized estimating equations were used to estimate risk ratios (RR) and 95% confidence intervals (CI) of financial hardship by COVID-19 status, and to assess the relationship between infection and Veteran age, VHA copay status, and comorbidity score, irrespective of COVID-19 status.

Results

Among 388 respondents, 67% reported at least one type of financial hardship since March 2020, with 21% reporting behavioral hardships and 64% material hardships; 8% reported severe-to-extreme health-related financial strain. Compared with uninfected matched comparators, Veterans with a history of COVID-19 had greater risks of severe-to-extreme health-related financial strain (RR: 4.0, CI: 1.4–11.2), taking less medication due to cost (RR: 2.9, 95% CI: 1.0–8.6), and having a loved one take time off work to care for them (RR: 1.9, CI: 1.1–3.6). Irrespective of COVID-19 status, Veterans aged < 65 years had a greater risk of most financial hardships compared with Veterans aged ≥ 65 years.

Conclusions

Health-related financial hardships such as taking less medication due to cost and severe-to-extreme health-related financial strain were more common among Veterans with a history of COVID-19 than among matched comparators. Strategies are needed to address health-related financial hardship after COVID-19.

Trial registration

NCT05394025, registered 05–27-2022.
Validation and psychometric evaluation of the Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS) among Czech adolescents using Item Response Theory
Authors: Hanzlová Radka , Kudrnáč Aleš
Published: August 2024

Background

The topic of adolescent mental health is currently a subject of much debate due to the increasing prevalence of mental health problems among this age group. Therefore, it is crucial to have high-quality and validated mental well-being measurement tools. While such tools do exist, they are often not tailored specifically to adolescents and are not available in Czech language. The aim of this study is to validate and test the Czech version of the Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS) on a large sample of Czech adolescents aged 15 to 18 years.

Methods

The analysis is based on data from the first wave of the Czech Education Panel Survey (CZEPS) and was mainly conducted using Item Response Theory (IRT), which is the most appropriate method for this type of analysis. Specifically, the Graded Response Model (GRM) was applied to the data. This comprehensive validation study also included reliability and three types of validity (construct, convergent and criterion) testing.

Results

The study found that the Czech version of the SWEMWBS for adolescents aged 15 to 18 years (N = 22,498) has good quality and psychometric properties. The data was analysed using the GRM model as it met the assumptions for the use of IRT. The estimated parameter values by GRM demonstrated good discriminant and informative power for all items, except for item 7, which showed poorer results compared to the others. However, excluding it from the scale would not enhance the overall quality of the scale. The five-category response scale functions effectively. Additionally, the results demonstrated high reliability, and all types of validity tested were also confirmed.

Conclusions

The Czech version of the SWEMWBS for adolescents has been validated as a psychometrically sound, reliable and valid instrument for measuring mental well-being. It can therefore be used with confidence in future studies.
Age assessment of unaccompanied foreign minors: an analyses of knowledge and practices among Italian pediatricians
Authors: Buonsenso Danilo , Ceccarelli Manuela , Camara Bettina , Angelone Donatella , Burzio Valentina , La Placa Simona , Valentini Piero ,   on behalf of GLNBM-SIP* and GLMM-SIMM**
Published: August 2024

Background

Increases in migration patterns in the recent years have led to a continuously growing number of unaccompanied foreign minors (UFMs) entering Italy. As part of processing and integration, age assessment is performed by pediatricians upon request of regulatory bodies. Updated guidelines for age estimation procedures were published in 2020 in order to prioritize the well-being of the minors and the accuracy of the assessment. Nonetheless, literature suggests that the recently established multidisciplinary approach has not yet been widely adopted by physicians.

Methods

A cross-sectional exploratory survey was distributed to pediatricians in Italy in order to gauge their range of experience with UFMs and age assessment protocols.

Results

In total 344 pediatricians participated in the survey, originating from varied regions in Italy. Out of pediatricians who reported conducting age assessment procedures (38.9%), only a small fraction (14.2%) confirmed being knowledgeable about the methodology. Instead, a significant portion (28.8% and 56.4%) either had partial awareness or lacked knowledge of these procedures. These responses significantly differed when comparing hospital and outpatient pediatricians or according to their geographical area of work (p <0.05).

Conclusion

Survey responses suggest that a gap in awareness and experience regarding a multidisciplinary approach to age estimations still exists, likely in part due to a lack of resources, especially at the regional level. In the future, efforts towards the education of professionals and mobilization of resources for investment in the field will be crucial for the improvement of work with UFMs and other migrant populations.
Melon: metagenomic long-read-based taxonomic identification and quantification using marker genes
Authors: Chen Xi , Yin Xiaole , Shi Xianghui , Yan Weifu , Yang Yu , Liu Lei , Zhang Tong
Published: August 2024

Long-read sequencing holds great potential for characterizing complex microbial communities, yet taxonomic profiling tools designed specifically for long reads remain lacking. We introduce Melon, a novel marker-based taxonomic profiler that capitalizes on the unique attributes of long reads. Melon employs a two-stage classification scheme to reduce computational time and is equipped with an expectation-maximization-based post-correction module to handle ambiguous reads. Melon achieves superior performance compared to existing tools in both mock and simulated samples. Using wastewater metagenomic samples, we demonstrate the applicability of Melon by showing it provides reliable estimates of overall genome copies, and species-level taxonomic profiles.
Feline leishmaniosis in the Mediterranean Basin: a multicenter study
Authors: Carbonara Mariaelisa , Iatta Roberta , Miró Guadalupe , Montoya Ana , Benelli Giovanni , Mendoza-Roldan Jairo Alfonso , Papadopoulos Elias , Lima Clara , Bouhsira Emilie , Nachum-Biala Yaarit , Decaro Nicola , Schunack Bettina , Baneth Gad , Otranto Domenico
Published: August 2024

Background

Cats are now recognized as competent hosts for Leishmania infantum and a blood source for sand fly vectors. Although canine leishmaniosis (CanL) is endemic in Mediterranean Basin countries, large-scale epidemiological studies are lacking for feline leishmaniosis (FeL). This study aimed to assess the prevalence of L. infantum infections, associated risk factors, clinical signs, and clinicopathological abnormalities in domestic cat populations from six Mediterranean Basin countries.

Methods

From 2019 to 2022, blood and serum samples of cats (n = 2067) living in Italy (n = 300), Greece (n = 297), Portugal (n = 295), France (n = 231), Israel (n = 313), and Spain (n = 631) were collected along with animal data (i.e., age, sex, breed, housing conditions, and geographical origin), clinical signs, and laboratory blood test parameters. Cats were grouped according to their age as kittens (up to 1 year), young (older than 1 and younger than 7 years), mature (between 7 and 10 years), and senior (older than 10 years). Serum samples were tested for L. infantum by immunofluorescence antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA), and blood samples of seropositive cats were tested for L. infantum kinetoplast deoxyribonucleic acid (kDNA). Viral infection by feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) was molecularly addressed in all cats enrolled. Statistical analysis was performed to evaluate the association between the risk of L. infantum infection and independent variables, and among co-infection of L. infantum with FIV and/or FeLV, clinical signs, and clinicopathological abnormalities.

Results

Overall, 17.3% (358/2067) of cats scored positive for L. infantum by serological tests. Specifically, 24.7% were from Portugal, 23.2% from Greece, 16.6% from Israel, 15% from Spain, 13.3% from France, and 12.6% from Italy. Leishmania infantum DNA was detected in 15 seropositive animals. Housing condition and FIV infection proved to be risk factors for FeL. Leishmania seropositivity was significantly associated with weight loss, lymphadenomegaly, gingivostomatitis, and oral ulcers, as well as with reduced albumin and albumin/globulin ratio, increased total globulins and total proteins, leukocytosis, and thrombocytosis.

Conclusions

This study provides, for the first time, a large-scale epidemiological survey on FeL and its clinical presentation, revealing that L. infantum circulates among domestic cats, especially shelter/free-roaming and FIV-infected animals, living in CanL endemic countries of the Mediterranean Basin.

Graphical Abstract
Evolutionary dependency of cancer mutations in gene pairs inferred by nonsynonymous-synonymous mutation ratios
Authors: Han Dong-Jin , Kim Sunmin , Lee Seo-Young , Moon Youngbeen , Kang Su Jung , Yoo Jinseon , Jeong Hye Young , Cho Hae Jin , Jeon Jeong Yang , Sim Byeong Chang , Kim Jaehoon , Lee Seungho , Xi Ruibin , Kim Tae-Min
Published: August 2024

Background

Determining the impact of somatic mutations requires understanding the functional relationship of genes acquiring mutations; however, it is largely unknown how mutations in functionally related genes influence each other.

Methods

We employed non-synonymous-to-synonymous or dNdS ratios to evaluate the evolutionary dependency (ED) of gene pairs, assuming a mutation in one gene of a gene pair can affect the evolutionary fitness of mutations in its partner genes as mutation context. We employed PanCancer- and tumor type-specific mutational profiles to infer the ED of gene pairs and evaluated their biological relevance with respect to gene dependency and drug sensitivity.

Results

We propose that dNdS ratios of gene pairs and their derived cdNS (context-dependent dNdS) scores as measure of ED distinguishing gene pairs either as synergistic (SYN) or antagonistic (ANT). Mutation contexts can induce substantial changes in the evolutionary fitness of mutations in the paired genes, e.g., IDH1 and IDH2 mutation contexts lead to substantial increase and decrease of dNdS ratios of ATRX indels and IDH1 missense mutations corresponding to SYN and ANT relationship with positive and negative cdNS scores, respectively. The impact of gene silencing or knock-outs on cell viability (genetic dependencies) often depends on ED, suggesting that ED can guide the selection of candidates for synthetic lethality such as TCF7L2-KRAS mutations. Using cell line-based drug sensitivity data, the effects of targeted agents on cell lines are often associated with mutations of genes exhibiting ED with the target genes, informing drug sensitizing or resistant mutations for targeted inhibitors, e.g., PRSS1 and CTCF mutations as resistant mutations to EGFR and BRAF inhibitors for lung adenocarcinomas and melanomas, respectively.

Conclusions

We propose that the ED of gene pairs evaluated by dNdS ratios can advance our understanding of the functional relationship of genes with potential biological and clinical implications.
Can heat conditions affect the heart rate responses, perception of effort, and technical performance of young male football players during small-sided games? a comparative study
Authors: Kang ZhiHui , Chen Zhongju , Liu GuiYang
Published: August 2024

Background

Soccer coaches often employ small-sided games (SSGs) to elicit both physiological and technical responses from players. However, numerous contextual factors can influence the outcomes of these games. This comparative study aimed to investigate how environmental temperature (< 21ºC and > 29ºC) impacts heart rate responses, perception of effort, and technical performance in young male football players during SSGs.

Methods

This study compares temperatures below 21ºC (∼ 20.4 ± 0.4ºC) with temperatures above 29ºC (∼ 29.7 ± 0.6ºC). This repeated measures study design involved 60 male football players at a trained/developmental level, selected from under-16 and under-19 teams. It aimed to assess the effects of the 3v3 format, conducted repeatedly under conditions of 21ºC and above 29ºC. Throughout the games, mean heart rate responses (HRmean), measured via heart rate sensors; rate of perceived exertion (RPE), assessed using the CR-10 Borg scale; and successful passes and lost balls, tracked through an ad hoc observational analysis tool, were monitored.

Results

No significant interactions were observed (time*age group) in meanHR (F = 0.159; p = 0.691; $$\:{\eta\:}_{p}^{2}$$=0.003), RPE (F=0.646; p=0.425; $$\:{\eta\:}_{p}^{2}$$=0.011), number of passes completed (F=0.204; p=0.654; $$\:{\eta\:}_{p}^{2}$$=0.003), and number of lost balls (F = 0.157; p = 0.694; $$\:{\eta\:}_{p}^{2}$$=0.003). Overall, significantly higher heart rate responses in mean HR (p<0.001) and RPE (p<0.001) were observed at temperatures above 29ºC, while significantly more passes were completed at temperatures below 21ºC (p<0.001).

Conclusions

Heat conditions significantly intensified the psychophysiological responses in players, concurrently leading to a significant impairment in the number of passes. Coaches should contemplate implementing mitigation strategies to avert performance declines during heat conditions when utilizing SSGs.
Association between thermogenic brown fat and genes under positive natural selection in circumpolar populations
Authors: Ishida Yuka , Matsushita Mami , Yoneshiro Takeshi , Saito Masayuki , Nakayama Kazuhiro
Published: August 2024

Background

Adaptation to cold was essential for human migration across Eurasia. Non-shivering thermogenesis through brown adipose tissue (BAT) participates in cold adaptation because some genes involved in the differentiation and function of BAT exhibit signatures of positive natural selection in populations at high latitudes. Whether these genes are associated with the inter-individual variability in BAT thermogenesis remains unclear. In this study, we evaluated the potential associations between BAT activity and single nucleotide polymorphisms (SNPs) in candidate gene regions in East Asian populations.

Methods

BAT activity induced by mild cold exposure was measured in 399 healthy Japanese men and women using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). The capacity for cold-induced thermogenesis and fat oxidation was measured in 56 men. Association analyses with physiological traits were performed for 11 SNPs at six loci (LEPR, ANGPTL8, PLA2G2A, PLIN1, TBX15-WARS2, and FADS1) reported to be under positive natural selection. Associations found in the FDG-PET/CT population were further validated in 84 healthy East Asian men and women, in whom BAT activity was measured using infrared thermography. Associations between the SNP genotypes and BAT activity or other related traits were tested using multiple logistic and linear regression models.

Results

Of the 11 putative adaptive alleles of the six genes, two intronic SNPs in LEPR (rs1022981 and rs12405556) tended to be associated with higher BAT activity. However, these did not survive multiple test comparisons. Associations with lower body fat percentage, plasma triglyceride, insulin, and HOMA-IR levels were observed in the FDG-PET/CT population (P < 0.05). Other loci, including TBX15-WARS2, which is speculated to mediate cold adaptation in Greenland Inuits, did not show significant differences in BAT thermogenesis.

Conclusions

Our results suggest a marginal but significant association between LEPR SNPs. However, robust supporting evidence was not established for the involvement of other loci under positive natural selection in cold adaptation through BAT thermogenesis in East Asian adults. Given the pleiotropic function of these genes, factors other than cold adaptation through BAT thermogenesis, such as diet adaptation, may contribute to positive natural selection at these loci.
Engineering microscopic delivery systems: a review of dissolving microneedle design, fabrication, and function
Authors: Dave Roshan , Shinde Swapnali , Kalayil Nisha , Budar Aarati
Published: August 2024

Dissolving microneedles (DMNs) represent an innovative advancement in drug delivery and skincare technologies, offering significant advantages compared to traditional needles. This paper presents an overview of the historical evolution of microneedles and the rise of dissolving types, exploring their definition, concept, and diverse clinical applications such as vaccinations, drug delivery, and skincare treatments. Design and manufacturing considerations cover the materials employed, fabrication techniques, and methods for characterizing DMNs, focusing on aspects like mechanical strength, dissolution rate, and delivery efficiency. The mechanism of action section examines skin penetration mechanics, the process of microneedle dissolution, controlled release of active compounds, and considerations of biocompatibility and safety. Recent developments in DMNs encompass technological advancements, improved delivery systems, and updates on clinical trials and studies. Challenges and opportunities in scaling up production, overcoming market adoption barriers, and future research directions are discussed, aiming to address unmet medical needs and expand applications. In summary, DMNs have the potential to transform drug delivery and skincare treatments, with ongoing advancements aimed at tackling current challenges and unlocking new opportunities for enhanced healthcare outcomes.

Graphical Abstract
Damage and restoration technology of historic buildings of brick and wood structures: a review
Authors: Hao Yunhong , Yao Zhonghe , Wu Rigen , Bao Yuanyuan
Published: August 2024

Historical buildings carry the key technologies and practical values throughout the development of architectural heritage. Investigating the restoration techniques for historical buildings under various forms of damage is an essential step in the conservation and utilization of these structures. Utilizing Web of Science (WOS) and China National Knowledge Infrastructure (CNKI) as the primary databases, this study employs the PRISMA methodology to search and screen relevant research literature. A comprehensive review of the retained literature is conducted, analyzing publication trends, co-citation networks of authors and keywords, among other characteristics. To enhance the visibility of restoration techniques, three-dimensional modeling diagrams are created using actual case information of material or component damage as a reference, thereby increasing the referential value of the review content on historical building restoration techniques. The study provides a thorough review of over 30 restoration techniques corresponding to 9 types of damage from the perspectives of historical building walls and wooden components. Additionally, new materials or technologies mentioned in the retrieved literature are categorized; for instance, in the context of moisture-proof treatment for brick masonry, traditional methods are explained, and new research on electrochemical desalination and lipid-based waterproof materials is discussed and evaluated. Finally, given the multifaceted value and the variable mechanisms of damage in historical buildings, an analysis of the restoration process and techniques reveals that the restoration of historical buildings is a complex interdisciplinary process. The development and implementation of restoration plans should adhere to the principles of cultural relic protection to ensure their reasonableness and effectiveness, while also considering sustainability and environmental adaptability to protect and reuse historical buildings, thus leveraging their cultural and historical values. Moreover, the advancement of restoration techniques for historical buildings in the future should be based on the inheritance of traditional craftsmanship and materials, while also integrating new technologies, materials, and concepts to enhance the applicability and efficiency of traditional techniques.
Effect of early administration of tetracosactide on mortality and host response in critically ill patients requiring rescue surgery: a sensitivity analysis of the STOPSHOCK phase 3 randomized controlled trial
Authors: Noera Giorgio , Bertolini Alfio , Calzà Laura , Gori Mercedes , Pitino Annalisa , D’Arrigo Graziella , Egan Colin Gerard , Tripepi Giovanni
Published: August 2024

Background

Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction. This was a sensitivity analysis of a drug (tetracosactide; TCS10) targeting melanocortin receptors (MCRs) in a phase 3 randomized controlled trial to improve cardiovascular surgical rescue outcome by reversing mortality and hemostatic disorders.

Methods

Sensitivity analysis was based on a randomized, two-arm, multicenter, double-blind, controlled trial. The Naïve Bayes classifier was performed by density-based sensitivity index for principal strata as proportional hazard model of 30-day surgical risk mortality according to European System for Cardiac Operative Risk Evaluation inputs-outputs in 100 consecutive cases (from August to September 2013 from Emilia Romagna region, Italy). Patients included an agent-based TCS10 group (10 mg, single intravenous bolus before surgery; n = 56) and control group (n = 44) and the association with cytokines, lactate, and bleeding-blood transfusion episodes with the prior-risk log-odds for mortality rate in time-to-event was analyzed.

Results

Thirty-day mortality was significantly improved in the TCS10 group vs. control group (0 vs. 8 deaths, P < 0.0001). Baseline levels of interleukin (IL)-6, IL-10, and lactate were associated with bleeding episodes, independent of TCS10 treatment [odds ratio (OR) = 1.90, 95% confidence interval (CI) 1.39–2.79; OR = 1.53, 95%CI 1.17–2.12; and OR = 2.92, 95%CI 1.40–6.66, respectively], while baseline level of Fms-like tyrosine kinase 3 ligand (Flt3L) was associated with lower bleeding rates in TCS10-treated patients (OR = 0.31, 95%CI 0.11–0.90, P = 0.03). For every 8 TCS10-treated patients, 1 bleeding case was avoided. Blood transfusion episodes were significantly reduced in the TCS10 group compared to the control group (OR = 0.32, 95%CI 0.14–0.73, P = 0.01). For every 4 TCS10-treated patients, 1 transfusion case was avoided.

Conclusions

Sensitivity index underlines the quality target product profile of TCS10 in the runway of emergency casualty care. To introduce the technology readiness level in real-life critically ill patients, further large-scale studies are required.

Trial registration

European Union Drug Regulating Authorities Clinical Trials Database (EudraCT Number: 2007-006445-41).
School-based intervention for anxiety using group cognitive behavior therapy in Pakistan: a feasibility randomized controlled trial
Authors: Ijaz Saman , Rohail Iffat , Irfan Shahid
Published: August 2024

Background

Anxiety and mood disorders are the main cause of illness in people under the age of 25, accounting for 45% of the global disease burden, whereas 4.6% of teenagers aged 15 to 19 are predicted to experience anxiety. Pakistan country, with a population of 200 million, has the worst mental health indicators and fewer than 500 psychiatrists. Despite the existence of various treatments for anxiety, this goes unrecognized and untreated. Due to a lack of awareness, evaluation, prevention, and interventional programs related to being implemented among adolescents in Pakistan, there is a rise in mental health issues in the earlier years of life. It calls for a critical need for indigenous, evidence-based interventions. The present study aimed to evaluate the feasibility of cognitive behavioral therapy (CBT)-based interventions to reduce anxiety symptoms among school children in Pakistan.

Methods

This study was a pre-post design, two-arm, single-blinded, feasibility, randomized controlled trial. Thirty-four participants (experimental group, n = 17; control group, n = 17) were recruited from four semi-government schools in Rawalpindi with a mean age of 15 (M = 15, SD = 0.73). Two instruments Beck Anxiety Inventory for Youth (BAI-Y II) and BASC-3 Behavioural and Emotional Screening System Student (BESS-SF) were used to assess the severity of symptoms. Participants in the intervention arm received eight-group therapy CBT sessions. A two-way factorial analysis was used to examine the efficacy of CBT in reducing symptom severity.

Results

This study’s findings showed that in comparison to the wait-list control group, CBT successfully improved anxiety symptoms among school children while enhancing their social skills.

Conclusion

This study will help improve the treatment for anxiety in Pakistan by prioritizing school-based intervention and group-based CBT intervention.

Trial registration

The trial has been registered at the American Economic Association’s registry for randomized controlled trials. RCT ID: AEARCTR-0009551. Registered 2022–07-04.
PSMA-PET/CT response after metastasis-directed radiotherapy of bone oligometastases in prostate cancer
Authors: Sheikh Gabriel T. , Trapp Christian , Schmidt-Hegemann Nina-Sophie , Buchner Alexander , Stief Christian G. , Unterrainer Marcus , Kunz Wolfgang G. , Cyran Clemens C. , Grawe Freba , Delker Astrid , Zacherl Mathias J. , Holzgreve Adrien , Unterrainer Lena M. , Brendel Matthias , Belka Claus , Li Minglun , Rogowski Paul
Published: August 2024

Objective

Bone metastases are very common in advanced prostate cancer and can sensitively be detected utilizing PSMA-PET/CT. Therefore, our goal was to evaluate the suitability of PSMA-PET/CT-guided metastasis-directed external beam radiotherapy (MDT) as treatment option for patients with biochemical recurrence and oligometastatic bone lesions.

Materials & methods

We retrospectively examined 32 prostate cancer patients with biochemical recurrence and PSMA-positive oligometastatic disease limited to the bone (n = 1–3). A total of 49 bone lesions were treated with MDT. All patients received a post-radiotherapy PSMA-PET/CT-Scan. Changes in SUVmax, PSMA-positive tumor volume per lesion and PSA, as well as the correlation between the PET/CT-interval and SUVmax response were calculated.

Results

MDT lead to a SUVmax decrease in 46/49 (94%) of the lesions. The median relative decline of SUVmax was 60.4%, respectively. Based on PSMA-positive lesion volume with a SUV cut-off of 4, 46/49 (94%) of lesions showed complete response, two (4%) partial response and one lesion (2%) was stable on PSMA-PET/CT after MDT. Most of the treated patients (56.3%) showed an initial PSA decline at three months and a PSA nadir of median 0.14 ng/ml after a median time of 3.6 months after MDT. The median relative PSA change at three months after MDT was 3.9%.

Conclusion

MDT is a very effective treatment modality for prostate cancer bone oligometastases and lesion response to MDT can be assessed using the (semi-)quantitative parameters SUVmax and PSMA-positive lesion volume with established SUV cut-offs.
Brazilian version of the “Primary Sjögren’s Syndrome - Quality of Life questionnaire (PSS-QoL)”: translation, cross-cultural adaptation and validation
Authors: Miyamoto Samira Tatiyama , Serrano Érica Vieira , Gianórdoli Ana Paula Espíndula , Altoé Lara Betini , Noronha Bianca Domingos , dos Santos Pedro Henrique Alves , Pedrini Ana Paula Truhlar , da Silva Nicole Reis Souza , Favarato Letícia Fonseca , Alochio Luíza Vallory , Tomé Weider Andrade , Lackner Angelika , Valim Valéria
Published: August 2024

Background

The Primary Sjögren’s Syndrome Quality of Life questionnaire (PSS-QoL) is the first specific instrument to assess health-related quality of life (HRQoL) in Sjögren’s disease (SjD). The aim is to translate and cross-culturally adapt the PSS-QoL into Brazilian Portuguese and to evaluate its psychometric properties.

Methods

The original English version was translated into Brazilian Portuguese by two native Brazilians who were proficient in the English language. The retranslation was conducted by two native Americans proficient in Brazilian Portuguese. A committee undertook an analysis of the translated and retranslated versions, resulting in the generation of the first Brazilian version, which was submitted to the cross-cultural adaptation phase. In this phase, 50 participants with SjD responded to the instrument in Stages I and II, resulting in the generation of the second and final Brazilian version. To assess the psychometric properties, demographic and clinical data were collected from 75 patients. The HRQoL questionnaires (final Brazilian version of the PSS-QoL, Short Form-36 Health Survey (SF-36) and EuroQoL-5 dimension (EQ-5D)) were completed. Construct validity was analyzed using the Pearson or Spearman correlation coefficient. Reliability was analyzed using Cronbach’s alpha and the intraclass correlation coefficient (ICC).

Results

Eight questions and one response item were revised due to an incomprehension rate of greater than 15% among the participants in the cross-cultural adaptation phase. The final Brazilian version of the PSS-QoL was validated, revealing a high correlation between the total score and functional capacity (r= −0.713, p < 0.001), and vitality (r= −0.770, p < 0. 001) and mental health (r= −0.742, p < 0.001) domains of the SF-36 and a moderate correlation with the other domains of the SF-36 and a moderate correlation with the EQ-5D-tto (r= −0.573, p < 0.001), and EQ-5D-VAS (r= −0.559, p < 0.001). The intraobserver (ICC = 0.939; Cronbach’s alpha = 0.964) and interobserver (ICC = 0.965; Cronbach’s alpha = 0.964) reliability of the total score showed very high consistency.

Conclusion

The Brazilian version of the PSS-QoL has been demonstrated to be a valid and reproducible instrument for the assessment of HRQoL in patients with SjD.
When concrete was considered sustainable: ecological crisis, technological transition and the prefabricated concrete rural houses in Jiangsu Province from 1961 to the 1980s
Authors: Chen Yichuan
Published: August 2024

This paper explores the creation, development, and dissemination of prefabricated concrete rural houses in Jiangsu Province in East China from 1961 to the 1980s, an example of the technological transition provoked by the depletion of forest and timber in China. Through archival research, fieldwork and interviews, the paper examines the two waves of design and dissemination of prefabricated concrete rural houses between 1961 and 1965 and their subsequent ‘vernacularisation’ in the 1970s and the 1980s. This research provides a twofold insight into the current scholarly debates surrounding built heritage and global climate change. On one hand, it addresses a historical context of concrete overuse in contemporary China, a matter of critical importance in relation to carbon emissions and global climate change. On the other hand, it offers a counter-argument to today's call for reintroducing timber structures in many places, as evidenced by the case of East China, where the widespread use of materials like concrete was primarily a consequence of the ecological crisis following decades of deforestation and timber resource depletion. In addition, the ‘vernacularisation’ of concrete structures manifested by this case still provides lessons for today’s efforts to popularise more eco-friendly construction materials and technologies, especially in rural areas, and the prefabricated concrete houses possess potential heritage values as trackers of ecological changes.