bluuebunny/crossref_metadata_2025 huggingface dataset:
Helminth parasites of the wild rabbit Oryctolagus cuniculus near Malham Tarn, Yorkshire, UK
Authors: Allan J.C. , Craig P.S. , Sherington J. , Rogan M.T. , Storey D.M. , Heath S. , Iball K.
Published: April 2024

Between 1992 and 1996, 95 rabbits from the immediate locality of Malham Tarn, North Yorkshire, UK were examined for the presence of helminth parasites. All the examinations took place in late September or October. Three species of nematodes, Graphidium strigosum, Passalurus ambiguusand Trichostrongylus retortaeformis and two species of cestodes, Taenia pisiformis and Cittotaenia pectinata were identified. There were no associations between helminth species richness and year of sampling, host weight or sex. A logistic model was fitted to the prevalence data from these helminths as was an over-dispersed Poisson model to the worm burden data. Graphidium strigosum was the most frequently identified species with an average prevalence of 78%. The mean prevalence and intensity of Graphidiuminfection were significantly effected by sampling year. The lower than normal rainfall recorded at the Tarn during the years 1995 and 1996 may have be one reason for this pattern. The worm burden of G. strigosum was significantly positively associated with rabbit body weight. The intensity of infection with P. ambiguus was significantly higher in female rabbits. There was a significant non-linear relationship between P. ambiguus worm burden and rabbit weight (P = 0.002) with worm burdens being highest in the 1000 g to 1499 g weight cohort. Trichostrongylus retortaeformis was only identified in 1994 and male rabbits harboured significantly higher worm burdens than females (48 vs. 7, P = 0.022). Over the five years, the average Taenia pisiformis prevalence was 31% and there was a significant positive association between worm burden and rabbit weight (P = 0.001). Cittotaenia pectinata had a prevalence of 37% over the whole study period with no interactions between prevalence or intensity and body weight, year of sampling or rabbit sex. All five helminths showed an overdispersed distribution with k values less than 1.
A molecular perspective on the genera Paragonimus Braun, Euparagonimus Chen and Pagumogonimus Chen
Authors: Blair D. , Wu B. , Chang Z.S. , Gong X. , Agatsuma T. , Zhang Y.N. , Chen S.H. , Lin J.X. , Chen M.G. , Waikagul J. , Guevara A.G. , Feng Z. , Davis G.M.
Published: April 2024

The status of the genera Euparagonimus Chen, 1963 and Pagumogonimus Chen, 1963 relative to Paragonimus Braun, 1899 was investigated using DNA sequences from the mitochondrial cytochrome c oxidase subunit I (CO1) gene (partial) and the nuclear ribosomal DNA second internal transcribed spacer (ITS2). In the phylogenetic trees constructed, the genus Pagumogonimus is clearly not monophyletic and therefore not a natural taxon. Indeed, the type species of Pagumogonimus,P. skrjabini from China, is very closely related to Paragonimusmiyazakii from Japan. The status of Euparagonimus is less obvious. Euparagonimus cenocopiosus lies distant from other lungflukes included in the analysis. It can be placed as sister to Paragonimus in some analyses and falls within the genus in others. A recently published morphological study placed E. cenocopiosus within the genus Paragonimus and probably this is where it should remain.
Three diplectanid monogeneans from marine finfish (Epinephelus spp.) in the Far East
Authors: Si Hla Bu Si , Leong T.S. , Wong S.Y. , Woo Y.S.N. , Foo R.W.T.
Published: April 2024

Two new species of diplectanid monogeneans, Diplectanum grouperi and Pseudorhabdosynochus coioidesis from the marine finfish Epinephelus coioides and E. aerolatus(Serranidae), cultured in floating cages in Malaysia, Indonesia and Hong Kong, were described and compared with P. lantauensis Beverley-Burton and Suriano, 1981 from the same hosts. There is no other close species sharing the features of Diplectanum grouperi. The possession of a copulatory organ with an open cup-like proximal part and a narrow tubular distal part is a main distinguished feature of D. grouperi. Pseudorhabdosynochus coioides is most closely related to P. epinepheli Yamaguti, 1938, but can be distinguished from it by the shape and the size of the haptor, hamuli, copulatory organ, the lack of a muscular bulbus ejaculatorius, a greater number of rows in the squamodiscs and the location of the testis. Pseudorhabdosynochus lantauensis from the present hosts differs from that described from the original hosts, Epinephelus brunneus and E. fario in the shape of the dorsal bar and vagina.
Nematocide activity of 6,7-diarylpteridines in three experimental models
Authors: Ochoa C. , Rodríguez M. , Domínguez L. , Saldaña J. , Di Maio R. , Alonso-Villalobos P. , Martínez Grueiro M.M.
Published: April 2024

The in vitro nematocide activity of seventeen 6,7-diarylpteridines has been tested using three different experimental models, Caenorhabditis elegans, Nippostrongylus brasiliensis and Heligmosomoides polygyrus. The method of evaluation of inhibition in the secretion of acetylcholinesterase by H. polygyrus seems to be the most indicated to avoid false positives. The in vivo activities, against Trichinella spiralis, of the most in vitro active pteridines have been assayed. All pteridine derivatives bearing 6,7-di-p-bromophenyl substituents have shown in vitronematocide activites in the three experimental models used. Amongst all the pteridines tested in vivo, only 2,4-pteridinedithione derivatives exhibited moderate activity.
Oral corticosteroid prescribing practice for chronic rhinosinusitis with nasal polyps among otorhinolaryngologists in Scotland: a nationwide survey
Authors: Misirovs Rasads , Hoey Gary , Lipworth Brian , Green Richard
Published: April 2024

Objective

Oral corticosteroids are used to treat exacerbations of chronic rhinosinusitis with nasal polyps. Oral corticosteroid prescribing practices vary as reported from national surveys in Italy, China, Canada and the USA.

Methods

A nationwide online survey of ENT doctors practicing in Scotland was conducted using Microsoft Forms.

Results

There was a 31 per cent response rate. The most common daily doses of oral corticosteroid courses were 25 mg and 40 mg with the lengths being 14 and 7 days, respectively. Seventy-seven per cent of respondents prescribed the same daily dose throughout the course. Rhinologists prescribed longer courses with a smaller daily dose of prednisolone. Only one respondent fully agreed that there were clear guidelines regarding the daily dose and the length of oral corticosteroid course in the treatment of chronic rhinosinusitis with nasal polyps.

Conclusion

The heterogeneity of oral corticosteroid prescribing practice in different countries, including Scotland, reveals the need for clear guidelines with a specific oral corticosteroid daily dose and length of the course.
Primary mode of communication for people with total laryngectomy in the UK: a cross-sectional survey
Authors: Woodman Sarah H , Govender Roganie , Baker Kate , Glaister Carol , Rowe Elizabeth A , Dunton Jane , Patterson Joanne M
Published: April 2024

Objective

This study aimed to report on the UK rate of surgical voice restoration usage and investigate the factors that influence its uptake.

Method

A national multicentre audit of people with total laryngectomy was completed over a six-month period (March to September 2020) in response to the coronavirus disease 2019 pandemic. This study is a secondary analysis of the data collected, focusing on the primary communication methods used by people with total laryngectomy.

Results

Data on surgical voice restoration were available for 1196 people with total laryngectomy; a total of 852 people with total laryngectomy (71 per cent) used surgical voice restoration. Another type of communication method was used by 344 people. The factors associated with surgical voice restoration in the multiple regression analysis were sex (p = 0.003), employment (employed vs not employed, p < 0.001) and time post-laryngectomy (p < 0.001).

Conclusion

This study provides an important benchmark for the current status of surgical voice restoration usage across the UK. It found that 71 per cent of people with total laryngectomy used surgical voice restoration as their primary communication method.
Automatic extrinsic calibration for structured light camera and repetitive LiDARs
Authors: Ge Yangtao , Yao Chen , Wang Zirui , Huang Bangzhen , Kang Haoran , Zhang Wentao , Jia Zhenzhong , Wu Jing
Published: April 2024

The integration of camera and LiDAR technologies has the potential to significantly enhance construction robots’ perception capabilities by providing complementary construction information. Structured light cameras (SLCs) are a desirable alternative as they provide comprehensive information on construction defects. However, fusing these two types of information depends largely on the sensors’ relative positions, which can only be established through extrinsic calibration. This paper introduces a novel calibration algorithm considering a customized board for SLCs and repetitive LiDARs, which are designed to facilitate the automation of construction robots. The calibration board is equipped with four symmetrically distributed hemispheres, whose centers are obtained by fitting the spheres and adoption with the geometric constraints. Subsequently, the spherical centers serve as reference features to estimate the relationship between the sensors. These distinctive features enable our proposed method to only require one calibration board pose and minimize human intervention. We conducted both simulation and real-world experiments to assess the performance of our algorithm. And the results demonstrate that our method exhibits enhanced accuracy and robustness.
Impact of dietary carbohydrate, fat or protein restriction on the human gut microbiome: a systematic review
Authors: Schoonakker Marjolein P. , van Peet Petra G. , van den Burg Elske L. , Numans Mattijs E. , Ducarmon Quinten R. , Pijl Hanno , Wiese Maria
Published: April 2024

Restriction of dietary carbohydrates, fat and/or protein is often used to reduce body weight and/or treat (metabolic) diseases. Since diet is a key modulator of the human gut microbiome, which plays an important role in health and disease, this review aims to provide an overview of current knowledge of the effects of macronutrient-restricted diets on gut microbial composition and metabolites. A structured search strategy was performed in several databases. After screening for inclusion and exclusion criteria, thirty-six articles could be included. Data are included in the results only when supported by at least three independent studies to enhance the reliability of our conclusions. Low-carbohydrate (<30 energy%) diets tended to induce a decrease in the relative abundance of several health-promoting bacteria, including Bifidobacterium, as well as a reduction in short-chain fatty acid (SCFA) levels in faeces. In contrast, low-fat diets (<30 energy%) increased alpha diversity, faecal SCFA levels and abundance of some beneficial bacteria, including Faecalibacterium prausnitzii. There were insufficient data to draw conclusions concerning the effects of low-protein (<10 energy%) diets on gut microbiota. Although the data of included studies unveil possible benefits of low-fat and potential drawbacks of low-carbohydrate diets for human gut microbiota, the diversity in study designs made it difficult to draw firm conclusions. Using a more uniform methodology in design, sample processing and sharing raw sequence data could foster our understanding of the effects of macronutrient restriction on gut microbiota composition and metabolic dynamics relevant to health. This systematic review was registered at https://www.crd.york.ac.uk/prospero as CRD42020156929.
Early life adversity is associated with greater similarity in neural representations of ambiguous and threatening stimuli
Authors: Saragosa-Harris Natalie M. , Guassi Moreira João F. , Waizman Yael , Sedykin Anna , Peris Tara S. , Silvers Jennifer A.
Published: April 2024

Exposure to early life adversity (ELA) is hypothesized to sensitize threat-responsive neural circuitry. This may lead individuals to overestimate threat in the face of ambiguity, a cognitive-behavioral phenotype linked to poor mental health. The tendency to process ambiguity as threatening may stem from difficulty distinguishing between ambiguous and threatening stimuli. However, it is unknown how exposure to ELA relates to neural representations of ambiguous and threatening stimuli, or how processing of ambiguity following ELA relates to psychosocial functioning. The current fMRI study examined multivariate representations of threatening and ambiguous social cues in 41 emerging adults (aged 18 to 19 years). Using representational similarity analysis, we assessed neural representations of ambiguous and threatening images within affective neural circuitry and tested whether similarity in these representations varied by ELA exposure. Greater exposure to ELA was associated with greater similarity in neural representations of ambiguous and threatening images. Moreover, individual differences in processing ambiguity related to global functioning, an association that varied as a function of ELA. By evidencing reduced neural differentiation between ambiguous and threatening cues in ELA-exposed emerging adults and linking behavioral responses to ambiguity to psychosocial wellbeing, these findings have important implications for future intervention work in at-risk, ELA-exposed populations.
A set-theoretic approach to algebraic L-domains
Authors: Zou Juan , Zhao Yuhan , Miao Cuixia , Wang Longchun
Published: April 2024

In this paper, the notion of locally algebraic intersection structure is introduced for algebraic L-domains. Essentially, every locally algebraic intersection structure is a family of sets, which forms an algebraic L-domain ordered by inclusion. It is shown that there is a locally algebraic intersection structure which is order-isomorphic to a given algebraic L-domain. This result extends the classic Stone’s representation theorem for Boolean algebras to the case of algebraic L-domains. In addition, it can be seen that many well-known representations of algebraic L-domains, such as logical algebras, information systems, closure spaces, and formal concept analysis, can be analyzed in the framework of locally algebraic intersection structures. Then, a set-theoretic uniformity across different representations of algebraic L-domains is established.
Safety, timing, and outcomes of early post-operative cardiac catheterisation following congenital heart surgery
Authors: Krzywda Karoline , Affolter Jeremy T. , Al-Hassan Darcie M. , Gibson William J. , Romans Ryan A. , Yeh Hung-Wen , Tieves Kelly S.
Published: April 2024

Objective:

The safety of early post-operative cardiac catheterisation has been described following congenital heart surgery. Optimal timing of early post-operative cardiac catheterisation remains uncertain. The aim of this study was to describe the safety of early post-operative cardiac catheterisation and its impact on cardiac ICU and hospital length of stay, duration of mechanical ventilation, and extracorporeal support.

Methods:

This single-centre retrospective cohort study compared clinical and outcome variables between “early” early post-operative cardiac catheterisation (less than 72 hours after surgery) and “late” early post-operative cardiac catheterisation (greater than 72 hours after surgery) groups using Chi-squared, Student’s t, and log-rank test (or appropriate nonparametric test).

Results:

In total, 132 patients were included, 22 (16.7%) “early” early post-operative cardiac catheterisation, and 110 (83.3%) “late” early post-operative cardiac catheterisation. Interventions were performed in 63 patients (51.5%), 7 (11.1%) early and 56 (88.9%) late. Complications of catheterisation occurred in seven (5.3%) patients, two early and five late. There were no major complications. Patients in the late group trended towards a longer stay in the cardiac ICU (19 days [7, 62] versus 11.5 days [7.2, 31.5], p = 0.6) and in the hospital (26 days [9.2, 68] versus 19 days [13.2, 41.8], p = 0.8) compared to the earlier group.

Conclusion:

“Early” early post-operative cardiac catheterisation was associated with an overall low rate of complications. Earlier catheterisations trended towards shorter cardiac ICU and hospital length of stays. Earlier catheterisations may lead to earlier recovery for patients not following an expected post-operative course.
Morphosyntactic underspecification affects the processing of verbal forms at different levels of abstraction in L1 and L2 German
Authors: Opitz Andreas , Bordag Denisa , Furgoni Alberto
Published: April 2024

Using a priming paradigm, we investigated the processing of overtly identical verb forms with different sets of morphosyntactic features in L1 and L2 German. We found that more specific functions of a verb (inflected verbs) were better primes for less specific verb functions (past participles) than vice versa. For L1 speakers, these priming asymmetries were observed regardless of whether the lexical verb was repeated in prime and target or not (i.e., priming also for abstract configurations). For L2 learners, a similar but not native-like asymmetric priming pattern was seen only with repetition of the lexical verb. It was absent when the verb was not repeated. We conclude that in L2, morphosyntactic information is processed more on a lexical, item-based level compared to L1. We discuss our results in the context of several accounts, e.g., Shallow Structure Hypothesis, Declarative Procedural Model and the Ontogenesis Model of the L2 Lexical Representation.
Social capital in the management of breast cancer in Lagos, Nigeria
Authors: Adejoh Samuel Ojima , Osazuwa Peter , Oyelowo Oluwakemi Tinuolaoluwa , Odey Maria Oyalowo , Tade Titi
Published: April 2024

Purpose

Breast cancer is the most common cancer in women worldwide, necessitating substantial social support during diagnosis and treatment. This study examines the role of social capital in breast cancer management, focusing on the experiences of patients.

Objectives

The objective of the study was to explore the role of social capital in breast cancer management among women living with breast cancer in Lagos, Nigeria.

Methods

Using a qualitative design, the study recruited 23 women with breast cancer receiving treatment at a teaching hospital in Lagos, Nigeria. Data were content analyzed to identify themes related to social capital.

Results

The study found that social capital, crucial for breast cancer patients’ emotional and instrumental support, stems from various sources such as relatives, immediate family, spouses, places of worship, friends, and neighbors. Effective coping and management of the condition were facilitated through this support network. However, assistance from places of worship, friends, and neighbors was only accessible to those who openly acknowledged their health conditions and had established connections with these social groups. Relationships led to support only when there was a disclosure of the health condition.

Significance of results

(1) This finding reinforces the importance of integrating social support mechanisms including family, friends, and community networks into breast cancer management programs. (2) The study identifies diverse sources of social capital, including relatives, family, spouses, places of worship, friends, and neighbors, stressing the need for tailored support networks. (3) Research reveals the link between health condition disclosure and support accessibility from groups like places of worship and friends, and it emphasizes creating stigma-free environments for patients to disclose health status comfortably. (4) The study highlights family involvement in breast cancer management as crucial for effective coping. Healthcare professionals should prioritize interventions strengthening family support systems. (5) Findings of stress community support for better breast cancer outcomes, advocating for initiatives like support groups and awareness campaigns to boost social capital and aid affected individuals.

Conclusion

The study emphasizes the significance of involving family members in the breast cancer management process and highlights the need for support systems within families and communities to facilitate better outcomes for breast cancer patients.
LPCAT2 inhibits colorectal cancer progression via the PRMT1/SLC7A11 axis
Authors: Cao Nan , Zhang Fangmei , Yin Jiang , Zhang Jianlei , Bian Xiqing , Zheng Guopei , Li Nan , Lin Ying , Luo Liyun
Published: April 2024

Colorectal cancer (CRC) has a high degree of heterogeneity and identifying the genetic information of individual tumor cells could help enhance our understanding of tumor biology and uncover potential therapeutic targets for CRC. In this study, we identified LPCAT2+ tumor cell populations with less malignancy than LPCAT2- tumor cells in human and mouse CRC tissues using scRNA-seq. Combining in vitro and in vivo experiments, we found that LPCAT2 could inhibit the proliferation of CRC cells by inducing ferroptosis. Mechanistically, LPCAT2 arrested PRMT1 in cytoplasm of CRC cells via regulating acetylation of PRMT1 at the K145 site. In turn, PRMT1 enhanced SLC7A11 promoter activity. Thus, LPCAT2 attenuated the positive regulatory effect of PRMT1 on SLC7A11 promoter. Notably, SLC7A11 acts as a ferroptosis regulator. Furthermore, in LPCAT2 knockout mice (LPCAT2−/−) colon cancer model, we found that LPCAT2−/− mice exhibited more severe lesions, while PRMT1 or SLC7A11 inhibitors delayed the progression. Altogether, we elucidated that LPCAT2 suppresses SLC7A11 expression by inhibiting PRMT1 nuclear translocation, thereby inducing ferroptosis in CRC cells. Moreover, inhibitors of the PRMT1/SLC7A11 axis could delay tumor progression in CRC with low LPCAT2 expression, making it a potentially effective treatment for CRC.
Facilitators and barriers to asylum seeker and refugee oral health care access: a qualitative systematic review
Authors: Wainman Nathan E. , Phillips Olivia R. , Morling Joanne R.
Published: April 2024

Objectives Asylum seekers and refugees (ASRs) encounter barriers when accessing oral health care (OHC). A qualitative systematic review was conducted to understand the perceptions, attitudes, behaviours and experiences of ASRs regarding their OHC. Themes were extracted to identify the barriers and facilitators ASRs face when accessing OHC.

Data sources PubMed, APA PsycInfo, Cochrane Database, Web of Science and CINAHL were searched on 4 and 5 October 2022.

Data selection Primary studies including ASRs of any age or nationality were included. Qualitative data of ASRs' lived experiences of oral health (OH) and accessing OHC were extracted. The Critical Appraisal Skills Programme quality appraisal tool was applied.

Data synthesis Data findings were extracted and meta-aggregation performed using inductive reasoning. A total of 13 primary qualitative studies were included. Three barriers were identified, including difficulty accessing treatments and appointments, cultural and language changes, and ASRs' lack of OHC knowledge or incongruous beliefs surrounding OH. Two facilitators were identified as good OH education and support from care providers or government.

Conclusions Decision-makers should adapt policy to facilitate access to OHC and educate ASRs on OH. More research is needed to understand the barriers and facilitators to OHC for other people groups who experience health inequalities.
Cell death dependent on holins LrgAB repressed by a novel ArsR family regulator CdsR
Authors: Zhang Xin , Chen Yuhan , Yan Tinglu , Wang Hengjie , Zhang Ruibin , Xu Yanrong , Hou Yujia , Peng Qi , Song Fuping
Published: April 2024

The cell death and survival paradox in various biological processes requires clarification. While spore development causes maternal cell death in Bacillus species, the involvement of other cell death pathways in sporulation remains unknown. Here, we identified a novel ArsR family transcriptional regulator, CdsR, and found that the deletion of its encoding gene cdsR causes cell lysis and inhibits sporulation. To our knowledge, this is the first report of an ArsR family transcriptional regulator governing cell death. We found that CdsR directly repressed lrgAB expression. Furthermore, lrgAB overexpression resulted in cell lysis without sporulation, akin to the cdsR mutant, suggesting that LrgAB, a holin-like protein, induces cell death in Bacillus spp. The lrgAB mutation increases abnormal cell numbers during spore development. In conclusion, we propose that a novel repressor is vital for inhibiting LrgAB-dependent cell lysis.
Gene pool preservation across time and space In Mongolian-speaking Oirats
Authors: Balinova Natalia , Hudjašov Georgi , Pankratov Vasili , Pennarun Erwan , Reidla Maere , Metspalu Ene , Batyrov Valery , Khomyakova Irina , Reisberg Tuuli , Parik Jüri , Dzhaubermezov Murat , Aiyzhy Elena , Balinova Altana , El’chinova Galina , Spitsyna Nailya , Khusnutdinova Elza , Metspalu Mait , Tambets Kristiina , Villems Richard , Kushniarevich Alena
Published: April 2024

The Oirats are a group of Mongolian-speaking peoples residing in Russia, China, and Mongolia, who speak Oirat dialects of the Mongolian language. Migrations of nomadic ethnopolitical formations of the Oirats across the Eurasian Steppe during the Late Middle Ages/early Modern times resulted in a wide geographic spread of Oirat ethnic groups from present-day northwestern China in East Asia to the Lower Volga region in Eastern Europe. In this study, we generate new genome-wide and mitochondrial DNA data for present-day Oirat-speaking populations from Kalmykia in Eastern Europe, Western Mongolia, and the Xinjiang region of China, as well as Issyk-Kul Sart-Kalmaks from Central Asia, and historically related ethnic groups from Altai, Tuva, and Northern Mongolia to study the genetic structure and history of the Oirats. Despite their spatial and temporal separation, small current population census, both the Kalmyks of Eastern Europe and the Oirats of Western Mongolia in East Asia are characterized by strong genetic similarity, high effective population size, and low levels of interpopulation structure. This contrasts the fine genetic structure observed today at a smaller geographic scale in traditionally sedentary populations, and is conditioned by high mobility and marriage practices (traditional strict exogamy) in nomadic groups. Conversely, the genetic profile of the Issyk-Kul Sart-Kalmaks suggests a distinct source(s) of genetic ancestry, along with indications of isolation and genetic drift compared to other Oirats. Our results also show that there was limited gene flow between the ancestors of the Oirats and the Altaians during the late Middle Ages.
Evaluation of 100 Dutch cases with 16p11.2 deletion and duplication syndromes; from clinical manifestations towards personalized treatment options
Authors: Vos Niels , Kleinendorst Lotte , van der Laan Liselot , van Uhm Jorrit , Jansen Philip R. , van Eeghen Agnies M. , Maas Saskia M. , Mannens Marcel M.A.M. , van Haelst Mieke M.
Published: April 2024

The 16p11.2 deletion syndrome is a clinically heterogeneous disorder, characterized by developmental delay, intellectual disability, hyperphagia, obesity, macrocephaly and psychiatric problems. Cases with 16p11.2 duplication syndrome have similar neurodevelopmental problems, but typically show a partial ‘mirror phenotype’ with underweight and microcephaly. Various copy number variants (CNVs) of the chromosomal 16p11.2 region have been described. Most is known about the ‘typical’ 16p11.2 BP4-BP5 (29.6–30.2 Mb; ~600 kb) deletions and duplications, but there are also several published cohorts with more distal 16p11.2 BP2-BP3 CNVs (28.8–29.0 Mb; ~220 kb), who exhibit clinical overlap. We assessed 100 cases with various pathogenic 16p11.2 CNVs and compared their clinical characteristics to provide more clear genotype-phenotype correlations and raise awareness of the different 16p11.2 CNVs. Neurodevelopmental and weight issues were reported in the majority of cases. Cases with distal 16p11.2 BP2-BP3 deletion showed the most severe obesity phenotype (73.7% obesity, mean BMI SDS 3.2). In addition to the more well defined typical 16p11.2 BP4-BP5 and distal 16p11.2 BP2-BP3 CNVs, we describe the clinical features of five cases with other, overlapping, 16p11.2 CNVs in more detail. Interestingly, four cases had a second genetic diagnosis and 18 cases an additional gene variant of uncertain significance, that could potentially help explain the cases’ phenotypes. In conclusion, we provide an overview of our Dutch cohort of cases with various pathogenic 16p11.2 CNVs and relevant second genetic findings, that can aid in adequately recognizing, diagnosing and counseling of individuals with 16p11.2 CNVs, and describe the personalized medicine for cases with these conditions.
Room-temperature quantum emission from interface excitons in mixed-dimensional heterostructures
Authors: Fang N. , Chang Y. R. , Fujii S. , Yamashita D. , Maruyama M. , Gao Y. , Fong C. F. , Kozawa D. , Otsuka K. , Nagashio K. , Okada S. , Kato Y. K.
Published: April 2024

The development of van der Waals heterostructures has introduced unconventional phenomena that emerge at atomically precise interfaces. For example, interlayer excitons in two-dimensional transition metal dichalcogenides show intriguing optical properties at low temperatures. Here we report on room-temperature observation of interface excitons in mixed-dimensional heterostructures consisting of two-dimensional tungsten diselenide and one-dimensional carbon nanotubes. Bright emission peaks originating from the interface are identified, spanning a broad energy range within the telecommunication wavelengths. The effect of band alignment is investigated by systematically varying the nanotube bandgap, and we assign the new peaks to interface excitons as they only appear in type-II heterostructures. Room-temperature localization of low-energy interface excitons is indicated by extended lifetimes as well as small excitation saturation powers, and photon correlation measurements confirm antibunching. With mixed-dimensional van der Waals heterostructures where band alignment can be engineered, new opportunities for quantum photonics are envisioned.
Multiscale architecture design of 3D printed biodegradable Zn-based porous scaffolds for immunomodulatory osteogenesis
Authors: Li Shuang , Yang Hongtao , Qu Xinhua , Qin Yu , Liu Aobo , Bao Guo , Huang He , Sun Chaoyang , Dai Jiabao , Tan Junlong , Shi Jiahui , Guan Yan , Pan Wei , Gu Xuenan , Jia Bo , Wen Peng , Wang Xiaogang , Zheng Yufeng
Published: April 2024

Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.
Protein disulfide isomerase cleaves allosteric disulfides in histidine-rich glycoprotein to regulate thrombosis
Authors: Lv Keyu , Chen Shuai , Xu Xulin , Chiu Joyce , Wang Haoqing J. , Han Yunyun , Yang Xiaodan , Bowley Sheryl R. , Wang Hao , Tang Zhaoming , Tang Ning , Yang Aizhen , Yang Shuofei , Wang Jinyu , Jin Si , Wu Yi , Schmaier Alvin H. , Ju Lining A. , Hogg Philip J. , Fang Chao
Published: April 2024

The essence of difference between hemostasis and thrombosis is that the clotting reaction is a highly fine-tuned process. Vascular protein disulfide isomerase (PDI) represents a critical mechanism regulating the functions of hemostatic proteins. Herein we show that histidine-rich glycoprotein (HRG) is a substrate of PDI. Reduction of HRG by PDI enhances the procoagulant and anticoagulant activities of HRG by neutralization of endothelial heparan sulfate (HS) and inhibition of factor XII (FXIIa) activity, respectively. Murine HRG deficiency (Hrg−/−) leads to delayed onset but enhanced formation of thrombus compared to WT. However, in the combined FXII deficiency (F12−/−) and HRG deficiency (by siRNA or Hrg−/−), there is further thrombosis reduction compared to F12−/− alone, confirming HRG’s procoagulant activity independent of FXIIa. Mutation of target disulfides of PDI leads to a gain-of-function mutant of HRG that promotes its activities during coagulation. Thus, PDI-HRG pathway fine-tunes thrombosis by promoting its rapid initiation via neutralization of HS and preventing excessive propagation via inhibition of FXIIa.
Rationally designed probiotics prevent shrimp white feces syndrome via the probiotics–gut microbiome–immunity axis
Authors: Sha Haonan , Lu Jiaqi , Chen Jiong , Xiong Jinbo
Published: April 2024

Increasing evidence infers that some complex diseases are attributed to co-infection with multiple pathogens, such as shrimp white feces syndrome (WFS); however, there is a lack of experimental evidence to validate such causal link. This deficiency further impedes rational design of probiotics to elicit desired benefits to shrimp WFS resistance. Herein, we validated the causal roles of Vibrio fluvialis, V. coralliilyticus and V. tubiashii (in a ratio of 7:2:1) in shrimp WFS etiology, which fully satisfied Koch’s postulates. Correspondingly, we precisely designed four antagonistic strains: Ruegeria lacuscaerulensis, Nioella nitratireducens, Bacillus subtilis and Streptomyces euryhalinus in a ratio of 4:3:2:1, which efficiently guarded against WFS. Dietary supplementation of the probiotics stimulated beneficial gut populations, streptomycin, short chain fatty acids, taurine metabolism potentials, network stability, tight junction, and host selection, while reducing turnover rate and average variation degree of gut microbiota, thereby facilitating ecological and mechanical barriers against pathogens. Additionally, shrimp immune pathways, such as Fcγ R-mediated phagocytosis, Toll-like receptor and RIG-I-like receptor signaling pathways conferring immune barrier, were activated by probiotics supplementation. Collectively, we establish an updated framework for precisely validating co-infection with multiple pathogens and rationally designing antagonistic probiotics. Furthermore, our findings uncover the underlying beneficial mechanisms of designed probiotics from the probiotics–gut microbiome–host immunity axis.
Enhancing watershed management through adaptive source apportionment under a changing environment
Authors: Wang Wenzhuo , Liu Guowangcheng , Zhang Yuhan , Wang Mingjing , Pan Yan , Meng Xinyi , Xiong Junfeng , Shen Zhenyao , Chen Lei
Published: April 2024

Effective watershed management hinges on understanding water sources and pollution origins. In the Hangbu Watershed of Chaohu Lake, China, we analyze pollution source patterns and propose an adaptive strategy. This adaptive strategy is defined as a flexible and dynamic approach that adjusts management practices and policies in response to evolving environmental conditions and emerging data on pollution sources. The analysis includes examining the trends, periodicity, and mutagenicity of pollution sources. The results demonstrated substantial variations in sources, with nitrogen and phosphorus. The adaptive approach enables prioritizing crucial pollution sources, with farmland identified as a significant contributor under varying conditions. Specific pollution sources with growth trends and control robustness have been recognized as vital contributors, even though their contributions to the nitrogen and phosphorus flux at the watershed outlets may not be the most prominent. The results of this study could guide the sustainable management of watersheds.
A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments
Authors: Chidley Christopher , Darnell Alicia M. , Gaudio Benjamin L. , Lien Evan C. , Barbeau Anna M. , Vander Heiden Matthew G. , Sorger Peter K.
Published: April 2024

Blocking the import of nutrients essential for cancer cell proliferation represents a therapeutic opportunity, but it is unclear which transporters to target. Here we report a CRISPR interference/activation screening platform to systematically interrogate the contribution of nutrient transporters to support cancer cell proliferation in environments ranging from standard culture media to tumours. We applied this platform to identify the transporters of amino acids in leukaemia cells and found that amino acid transport involves high bidirectional flux dependent on the microenvironment composition. While investigating the role of transporters in cystine starved cells, we uncovered a role for serotonin uptake in preventing ferroptosis. Finally, we identified transporters essential for cell proliferation in subcutaneous tumours and found that levels of glucose and amino acids can restrain proliferation in that environment. This study establishes a framework for systematically identifying critical cellular nutrient transporters, characterizing their function and exploring how the tumour microenvironment impacts cancer metabolism.
Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers
Authors: Acanda De La Rocha Arlet M. , Berlow Noah E. , Fader Maggie , Coats Ebony R. , Saghira Cima , Espinal Paula S. , Galano Jeanette , Khatib Ziad , Abdella Haneen , Maher Ossama M. , Vorontsova Yana , Andrade-Feraud Cristina M. , Daccache Aimee , Jacome Alexa , Reis Victoria , Holcomb Baylee , Ghurani Yasmin , Rimblas Lilliam , Guilarte Tomás R. , Hu Nan , Salyakina Daria , Azzam Diana J.
Published: April 2024

Children with rare, relapsed or refractory cancers often face limited treatment options, and few predictive biomarkers are available that can enable personalized treatment recommendations. The implementation of functional precision medicine (FPM), which combines genomic profiling with drug sensitivity testing (DST) of patient-derived tumor cells, has potential to identify treatment options when standard-of-care is exhausted. The goal of this prospective observational study was to generate FPM data for pediatric patients with relapsed or refractory cancer. The primary objective was to determine the feasibility of returning FPM-based treatment recommendations in real time to the FPM tumor board (FPMTB) within a clinically actionable timeframe (<4 weeks). The secondary objective was to assess clinical outcomes from patients enrolled in the study. Twenty-five patients with relapsed or refractory solid and hematological cancers were enrolled; 21 patients underwent DST and 20 also completed genomic profiling. Median turnaround times for DST and genomics were within 10 days and 27 days, respectively. Treatment recommendations were made for 19 patients (76%), of whom 14 received therapeutic interventions. Six patients received subsequent FPM-guided treatments. Among these patients, five (83%) experienced a greater than 1.3-fold improvement in progression-free survival associated with their FPM-guided therapy relative to their previous therapy, and demonstrated a significant increase in progression-free survival and objective response rate compared to those of eight non-guided patients. The findings from our proof-of-principle study illustrate the potential for FPM to positively impact clinical care for pediatric and adolescent patients with relapsed or refractory cancers and warrant further validation in large prospective studies. ClinicalTrials.gov registration: NCT03860376.
brainlife.io: a decentralized and open-source cloud platform to support neuroscience research
Authors: Hayashi Soichi , Caron Bradley A. , Heinsfeld Anibal Sólon , Vinci-Booher Sophia , McPherson Brent , Bullock Daniel N. , Bertò Giulia , Niso Guiomar , Hanekamp Sandra , Levitas Daniel , Ray Kimberly , MacKenzie Anne , Avesani Paolo , Kitchell Lindsey , Leong Josiah K. , Nascimento-Silva Filipi , Koudoro Serge , Willis Hanna , Jolly Jasleen K. , Pisner Derek , Zuidema Taylor R. , Kurzawski Jan W. , Mikellidou Kyriaki , Bussalb Aurore , Chaumon Maximilien , George Nathalie , Rorden Christopher , Victory Conner , Bhatia Dheeraj , Aydogan Dogu Baran , Yeh Fang-Cheng F. , Delogu Franco , Guaje Javier , Veraart Jelle , Fischer Jeremy , Faskowitz Joshua , Fabrega Ricardo , Hunt David , McKee Shawn , Brown Shawn T. , Heyman Stephanie , Iacovella Vittorio , Mejia Amanda F. , Marinazzo Daniele , Craddock R. Cameron , Olivetti Emanuale , Hanson Jamie L. , Garyfallidis Eleftherios , Stanzione Dan , Carson James , Henschel Robert , Hancock David Y. , Stewart Craig A. , Schnyer David , Eke Damian O. , Poldrack Russell A. , Bollmann Steffen , Stewart Ashley , Bridge Holly , Sani Ilaria , Freiwald Winrich A. , Puce Aina , Port Nicholas L. , Pestilli Franco
Published: April 2024

Neuroscience is advancing standardization and tool development to support rigor and transparency. Consequently, data pipeline complexity has increased, hindering FAIR (findable, accessible, interoperable and reusable) access. brainlife.io was developed to democratize neuroimaging research. The platform provides data standardization, management, visualization and processing and automatically tracks the provenance history of thousands of data objects. Here, brainlife.io is described and evaluated for validity, reliability, reproducibility, replicability and scientific utility using four data modalities and 3,200 participants.
High-resolution freshwater dissolved calcium and pH data layers for Canada and the United States
Authors: Guerin Andrew J. , Weise Andréa M. , Chu Jackson W. F. , Wilcox Mark A. , Greene Erin Sowerby , Therriault Thomas W.
Published: April 2024

Freshwater ecosystems are biologically important habitats that provide many ecosystem services. Calcium concentration and pH are two key variables that are linked to multiple chemical processes in these environments, influence the biology of organisms from diverse taxa, and can be important factors affecting the distribution of native and non-native species. However, it can be challenging to obtain high-resolution data for these variables at regional and national scales. To address this data gap, water quality data for lakes and rivers in Canada and the continental USA were compiled and used to generate high-resolution (10 × 10 km) interpolated raster layers, after comparing multiple spatial interpolation approaches. This is the first time that such data have been made available at this scale and resolution, providing a valuable resource for research, including projects evaluating risks from environmental change, pollution, and invasive species. This will aid the development of conservation and management strategies for these vital habitats.
An open source knowledge graph ecosystem for the life sciences
Authors: Callahan Tiffany J. , Tripodi Ignacio J. , Stefanski Adrianne L. , Cappelletti Luca , Taneja Sanya B. , Wyrwa Jordan M. , Casiraghi Elena , Matentzoglu Nicolas A. , Reese Justin , Silverstein Jonathan C. , Hoyt Charles Tapley , Boyce Richard D. , Malec Scott A. , Unni Deepak R. , Joachimiak Marcin P. , Robinson Peter N. , Mungall Christopher J. , Cavalleri Emanuele , Fontana Tommaso , Valentini Giorgio , Mesiti Marco , Gillenwater Lucas A. , Santangelo Brook , Vasilevsky Nicole A. , Hoehndorf Robert , Bennett Tellen D. , Ryan Patrick B. , Hripcsak George , Kahn Michael G. , Bada Michael , Baumgartner William A. , Hunter Lawrence E.
Published: April 2024

Translational research requires data at multiple scales of biological organization. Advancements in sequencing and multi-omics technologies have increased the availability of these data, but researchers face significant integration challenges. Knowledge graphs (KGs) are used to model complex phenomena, and methods exist to construct them automatically. However, tackling complex biomedical integration problems requires flexibility in the way knowledge is modeled. Moreover, existing KG construction methods provide robust tooling at the cost of fixed or limited choices among knowledge representation models. PheKnowLator (Phenotype Knowledge Translator) is a semantic ecosystem for automating the FAIR (Findable, Accessible, Interoperable, and Reusable) construction of ontologically grounded KGs with fully customizable knowledge representation. The ecosystem includes KG construction resources (e.g., data preparation APIs), analysis tools (e.g., SPARQL endpoint resources and abstraction algorithms), and benchmarks (e.g., prebuilt KGs). We evaluated the ecosystem by systematically comparing it to existing open-source KG construction methods and by analyzing its computational performance when used to construct 12 different large-scale KGs. With flexible knowledge representation, PheKnowLator enables fully customizable KGs without compromising performance or usability.
OCTDL: Optical Coherence Tomography Dataset for Image-Based Deep Learning Methods
Authors: Kulyabin Mikhail , Zhdanov Aleksei , Nikiforova Anastasia , Stepichev Andrey , Kuznetsova Anna , Ronkin Mikhail , Borisov Vasilii , Bogachev Alexander , Korotkich Sergey , Constable Paul A. , Maier Andreas
Published: April 2024

Optical coherence tomography (OCT) is a non-invasive imaging technique with extensive clinical applications in ophthalmology. OCT enables the visualization of the retinal layers, playing a vital role in the early detection and monitoring of retinal diseases. OCT uses the principle of light wave interference to create detailed images of the retinal microstructures, making it a valuable tool for diagnosing ocular conditions. This work presents an open-access OCT dataset (OCTDL) comprising over 2000 OCT images labeled according to disease group and retinal pathology. The dataset consists of OCT records of patients with Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), Epiretinal Membrane (ERM), Retinal Artery Occlusion (RAO), Retinal Vein Occlusion (RVO), and Vitreomacular Interface Disease (VID). The images were acquired with an Optovue Avanti RTVue XR using raster scanning protocols with dynamic scan length and image resolution. Each retinal b-scan was acquired by centering on the fovea and interpreted and cataloged by an experienced retinal specialist. In this work, we applied Deep Learning classification techniques to this new open-access dataset.