bluuebunny/crossref_metadata_2025 huggingface dataset:
Moral distress and associated factors among nurses working in central Ethiopia: a cross-sectional study
Authors: Getahun Mihiret Shawel , Gurara Abenet Menene , Bekele Nardos Tilahun , Kumbi Mahlet Mesfin , Aboye Israel Bekele , Zeleke Mahlet Daniel , Leta Milko Dersu , Kebede Yabets Tesfaye , Fikreyesus Yami Mihiret , Negussie Yohannes Mekuria
Published: March 2024

Background

Moral distress is recognized as a problem affecting nurse professionals globally. Unaddressed moral distress harms nurses’ physical and mental health, the quality of patient care, and the performance of healthcare teams and organizations. However, evidence on the magnitude and risk factors of moral distress is limited in Ethiopia in general and in the study area in particular. Thus, this study aimed to assess the magnitude of moral distress and associated factors among nurses working in Adama Comprehensive Specialized Hospital Medical College, central Ethiopia, 2023.

Methods

A facility-based cross-sectional study was conducted from January 1 to 30, 2023, with 219 nurses. A simple random sampling technique was employed to select the study participants. A self-administered structured questionnaire was used for data collection and Moral Distress Scale-Revised (MDS-R) was used to assess moral distress. Data were checked, coded, and entered into Epi info version 7, and then exported to the Statistical Package for Social Science version 26 for analysis. Bivariable and multivariable logistic regression analyses were carried out to identify factors associated with moral distress. The odds ratio with its 95% confidence interval was used as a measure of association and statistical significance was declared at a p-value < 0.05.

Result

A total of 212 nurses participated in the analysis making the response rate 96.8%. The magnitude of moral distress was 86.8% (95% CI 82.1%, 91.0%). Perceived powerlessness (AOR = 6.08; 95% CI 1.69, 11.8), lack of confidence (AOR = 7.08; 95% CI 2.05–14.41), inadequate staffing (AOR = 12.46; 95% CI 3.28,15.1), and perceived weak organizational support (AOR = 11.59; 95% CI 2.8,17.33) were significantly associated with moral distress.

Conclusion

The magnitude of moral distress was high among nurses in the study setting. Perceived powerlessness, lack of confidence, inadequate staffing, and perceived weak organizational support were independent determinants of moral distress. Thus, creating adequate number of staff, and establishing acceptable organizational policies are ways to reduce moral distress.
South Korean Migrants in China
Authors: Ma Xiao
Published: March 2024

This book is an ethnographic account of education and migration from the perspective of three groups of South Koreans in contemporary China: migrant parents, children/students, and educational agents. The book reveals how these temporary migrants make choices, plan their trajectories and engage with the authorities, both in China and South Korea. Migrant subjectivities among these groups are driven by and respond to the education-migration regimes of both the sending and receiving countries. As 'people in between', they occupy flexible and multiple positionalities that are transnationally distributed. However, paradoxically, they experience a juxtaposition of privilege, integration and separation, which is indicative of the Chinese style of internationalisation. The book adds weight to the argument that China is a temporary destination for foreigners and not one for long-term settlement.
Cross-cousin marriage among Tsimane forager–horticulturalists during demographic transition and market integration
Authors: Dalzero Arianna , Beheim Bret A. , Kaplan Hillard , Stieglitz Jonathan , Hooper Paul L. , Ross Cody T. , Gurven Michael , Lukas Dieter
Published: March 2024

Although still prevalent in many human societies, the practice of cousin marriage has precipitously declined in populations undergoing rapid demographic and socioeconomic change. However, it is still unclear whether changes in the structure of the marriage pool or changes in the fitness-relevant consequences of cousin marriage more strongly influence the frequency of cousin marriage. Here, we use genealogical data collected by the Tsimane Health and Life History Project to show that there is a small but measurable decline in the frequency of first cross-cousin marriage since the mid-twentieth century. Such changes are linked to concomitant changes in the pool of potential spouses in recent decades. We find only very modest differences in fitness-relevant demographic measures between first cousin and non-cousin marriages. These differences have been diminishing as the Tsimane have become more market integrated. The factors that influence preferences for cousin marriage appear to be less prevalent now than in the past, but cultural inertia might slow the pace of change in marriage norms. Overall, our findings suggest that cultural changes in marriage practices reflect underlying societal changes that shape the pool of potential spouses.
Fundamental Rights and Limited Possibilities: The Proviso of the Possible in European Fundamental Rights Doctrine
Authors: Munaretto Lino
Published: March 2024

Fundamental rights to positive state action are costly. An allocation in favor of one individual rightsholder always results in lower allocations in favor of others. The dominant approach in fundamental rights doctrine assumes these conflicts can be resolved judicially by balancing competing rights and other public needs. In practice, carrying out an in-depth balancing in resource allocation cases proves challenging but constitutional courts developed different strategies and concepts to deal with costly rights. The European Court of Human Rights applies a “wide” margin of appreciation and requires that positive state obligations do “not impose an impossible or disproportionate burden on the authorities.” Following the German Federal Constitutional Court, several constitutional courts have applied a concept known as the “proviso of the possible.” The proviso of the possible constrains positive rights and results in a wide margin of discretion granted to political authorities. This article attempts to investigate the specific meaning of the “proviso of the possible” in the context of European fundamental rights law by comparing it against alternative doctrinal concepts. The investigation aims to identify common legal principles and methods to deal with fundamental rights conflicts over scarce public resources.
Partisanship and Political Socialization in Electoral Autocracies
Authors: LETSA NATALIE WENZELL
Published: March 2024

In electoral autocracies, why do some people actively support political parties while others choose to not get involved in politics? Further, what differentiates those who choose to support the ruling party from those who support the opposition? Existing research has proposed that people support ruling parties primarily to extract economic benefits from the state while people support opposition parties primarily for ideological reasons. However, we lack a unified theory of partisanship, leading to indeterminant predictions about the individual predictors of partisanship. This article instead considers the social nature of partisanship in authoritarian regimes. Qualitative data collected in Cameroon highlight different processes of political socialization in an autocratic context, and data from an original survey show not only that partisan homogeneity in social networks is highly predictive of individual-level partisanship but also, at least to some extent, that partisanship can be contagious through the process of socialization within these networks.
On the virtues of neutrality
Authors: Anderson James N.
Published: March 2024

Jc Beall's Divine Contradiction proposes a bold response to the so-called ‘logical’ problems of the Trinity: we should admit without embarrassment that divine reality is flat-out contradictory. Beall defends his proposal against a wide range of objections and contends that it enjoys various philosophical and theological virtues, including the virtues of metaphysical and epistemological neutrality. While I agree that ceteris paribus these are desirable, I question whether the possession of these virtues really gives Beall's approach any advantage over its competitors when the chips are finally counted.
Zariski dense surface subgroups in with odd
Authors: GARCÍA CARMEN GALAZ
Published: March 2024

For odd n we construct a path
$\rho\;:\;\thinspace \Pi_1(S) \to SL(n\mathbb{R})$
of discrete, faithful, and Zariski dense representations of a surface group such that
$\rho_t(\Pi_1(S)) \subset SL(n,\mathbb{Q})$
for every
$t\in \mathbb{Q}$
.
Forest cover and environment type shape functional diversity of insectivorous birds within the Brazilian Atlantic Forest
Authors: Manzoli Enzo C , Gaspar Lucas P , Melo Marcos A , Adorno Bruno FCB , Ribeiro Milton C , Piratelli Augusto J
Published: March 2024

Tropical insectivorous birds comprise a diverse group that has a distinct response to habitat degradation. However, knowledge on birds’ ecological functions and their large-scale functional responses to human impacts across various habitats is scarce. We sampled 22 1-km-radius buffer landscapes within the Cantareira-Mantiqueira region (south-east Brazil), including native forests, pastures and marshes, to assess how landscape and habitat characteristics might affect insectivorous birds within the Brazilian Atlantic Forest. We studied whether bird species and functional diversity might respond to habitat turnover and nestedness and to native forest cover using generalized linear mixed models. We found negative effects of increased native forest cover on functional diversity indices. Bird communities in pastures show more nestedness, whereas marsh areas exhibit higher turnover. Forest areas receive a balanced contribution from both nestedness and turnover. These results are attributable to the predominantly secondary growth and early successional stages of the native forest fragments in the region, emphasizing the connection between landscape characteristics, habitat types and bird functional diversity in the Brazilian Atlantic Forest.
Asylum Marginalisation Renewed: ‘Vulnerability Backsliding’ at the European Court of Human Rights
Authors: Hudson Ben
Published: March 2024

It is now over ten years since the European Court of Human Rights (ECtHR or Court) first established that asylum seekers are inherently and particularly vulnerable on account of their very situation as asylum seekers. This occurred in its Grand Chamber judgment in the case of M.S.S. v Belgium and Greece. This article critically examines the Court’s subsequent asylum jurisprudence through the lens of vulnerability. The analysis reveals that the Court has engaged in ‘vulnerability backsliding’. Specifically, it traces the ways in which the Court has surreptitiously reversed the very principle of asylum vulnerability it itself established in M.S.S. The consequence of this backsliding is not only that the judicially recognised concept of asylum vulnerability is undermined, but that some of the most vulnerable applicants that come before the Court suffer renewed marginalisation, and, in some circumstances, exclusion from the ‘special protection’ to which they were previously afforded courtesy of M.S.S.
Carers’ and therapists’ views of internet-delivered guided self-help acceptance and commitment therapy for family carers of people with dementia (iACT4CARERS): a qualitative study in the context of ethnic minority families
Authors: Kishita Naoko , Czyznikowska Barbara , Riggey Megan , Van Hout Elien , Richmond Erica , Gould Rebecca L. , McCracken Lance M. , Farquhar Morag
Published: March 2024

This study aimed to explore the views of family carers of people living with dementia from ethnic minority groups and their therapists on internet-delivered, self-help acceptance and commitment therapy for family carers (iACT4CARERS), enhanced with additional therapist guidance. To achieve this, a qualitative approach with semi-structured interviews was employed with ethnic minority carers who completed Enhanced iACT4CARERS (n=9) and therapists who supported them throughout the programme (n=5). The interviews were audio-recorded, transcribed and analysed using framework analysis. Four over-arching themes were identified: (1) Value of the programme to ethnic minority carers, (2) Barriers for ethnic minority carers, (3) Sense of connectedness through written feedback, and (4) Sense of connectedness through one-to-one sessions. Theme 1 reflected that ethnic minority carers valued ACT techniques, highlighting their usefulness and simplicity, leading to perceived benefits. Theme 2 revealed the irrelevance of examples provided of carer experiences throughout the programme due to differences in family carers’ experiences of providing care within ethnic minority communities. Theme 3 highlighted that carers’ engagement with the programme was facilitated by feelings of validation and encouragement received from their therapist via weekly written feedback. Finally, Theme 4 highlighted that additional one-to-one support sessions allowed both carers and therapists to develop strong therapeutic relationships. This enhanced subsequent text-based online interactions, allowing carers to be more open and engaged. Also, therapists reported that a strong sense of connectedness helped them to tailor their feedback. Enhanced iACT4CARERS that uses carers’ experiences more relevant to ethnic minority communities may be more acceptable.

Key learning aims

(1)

To understand the views of family carers of people living with dementia from ethnic minority groups and their therapists on internet-delivered, self-help acceptance and commitment therapy (ACT), which has been found to be feasible and acceptable with White British carers.

(2)

To understand whether additional one-to-one support can help develop effective therapeutic relationships and thus improve the experiences of carers in completing the programme.

(3)

To learn whether any cultural adaptations are needed to improve the acceptability of internet-delivered self-help ACT among this population.
Requesting conflicts of interest declarations from the European Medicines Agency: 3-year follow-up status
Authors: Boesen K. , Gøtzsche P. C. , Ioannidis J. P. A.
Published: March 2024

Aims

We have previously described the European Medicines Agency’s (EMA) and the US Food and Drug Administration’s guidelines, each for a specific psychiatric indication, on how to design pivotal drug trials used in new drug applications. Here, we report on our efforts over 3 years to retrieve conflicts of interest declarations from EMA. We wanted to assess potential internal industry influence judged as the proportion of guideline committee members with industry conflicts of interest.

Methods

We submitted Freedom of Information requests in February 2020 to access EMA’s lists of committee members (and their declared conflicts of interest) involved in drafting the 13 ‘Clinical efficacy and safety’ guidelines available on EMA’s website pertaining to psychiatric indications. In our request, we did not specify the exact EMA committees. Here, we describe the received documents and report the proportion of members with industry interests (i.e. defined as any financial industry relationship). It is a follow-up paper to our first report (http://doi.org/10.1017/S2045796021000147).

Results

After 2 years and 9 months (November 2022), the EMA sent us member lists and corresponding conflicts of interest declarations from the Committee for Medicinal Products for Human use (CHMP) from 2012, 2013 and 2017. These member lists pertained to 3 of the 13 requested guidelines (schizophrenia, depression and autism spectrum disorder). The 10 remaining guidelines were published before 2011 and EMA stated that they needed to require permission from their expert members (with unknown retrieval rate) and foresaw excessive workload and long wait. Therefore, we withdrew our request. The CHMPs from 2012, 2013 and 2017 had from 34 to 36 members; 39%–44% declared any interests and we judged 14%–18% as having industry interests. For the schizophrenia guideline, we identified two members with industry interests to companies who submitted feedback on the guideline. We did not receive declarations from the Central Nervous System (CNS) Working Party, the CHMP appointed expert group responsible for drafting and incorporating feedback into the guidelines.

Conclusions

After almost 3 years, we received information, which only partly addressed our request. We recommend EMA to improve transparency by publishing the author names and their corresponding conflicts of interest declarations directly in the ‘Clinical efficacy and safety’ guidelines and to not remove conflicts of interest declarations after 1 year from their website to reduce the risk of stealth corporate influence during the development of these influential guidelines.
Can Glacial Sea‐Level Drop‐Induced Gas Hydrate Dissociation Cause Submarine Landslides?
Authors: Liu Jinlong , Gupta Shubhangi , Rutqvist Jonny , Ma Yikai , Wang Shuhong , Wan Kuiyuan , Fan Chaoyan , Yan Wen
Published: March 2024

We conducted two‐dimensional numerical simulations to investigate the mechanisms underlying the strong spatiotemporal correlation observed between submarine landslides and gas hydrate dissociation due to glacial sea‐level drops. Our results suggest that potential plastic deformation or slip could occur at localized and small scales in the shallow‐water portion of the gas hydrate stability zone (GHSZ). This shallow‐water portion of the GHSZ typically lies within the area enclosed by three points: the BGHSZ–seafloor intersection, the seafloor at ∼600 m below sea level (mbsl), and the base of the GHSZ (BGHSZ) at ∼1,050 mbsl in low‐latitude regions. The deep BGHSZ (>1,050 mbsl) could not slip; therefore, the entire BGHSZ was not a complete slip surface. Glacial hydrate dissociation alone is unlikely to cause large‐scale submarine landslides. Observed deep‐water (much greater than 600 mbsl) turbidites containing geochemical evidence of glacial hydrate dissociation potentially formed from erosion or detachment in the GHSZ pinch‐out zone.
How comparable are patient outcomes in the “real-world” with populations studied in pivotal AML trials?
Authors: Tiong Ing Soo , Wall Meaghan , Bajel Ashish , Kalro Akash , Fleming Shaun , Roberts Andrew W. , Thiagarajah Nisha , Chua Chong Chyn , Latimer Maya , Yeung David , Marlton Paula , Johnston Amanda , Enjeti Anoop , Fong Chun Yew , Cull Gavin , Larsen Stephen , Kennedy Glen , Schwarer Anthony , Kipp David , Ramanathan Sundra , Verner Emma , Tiley Campbell , Morris Edward , Hahn Uwe , Moore John , Taper John , Purtill Duncan , Warburton Pauline , Stevenson William , Murphy Nicholas , Tan Peter , Beligaswatte Ashanka , Mutsando Howard , Hertzberg Mark , Shortt Jake , Szabo Ferenc , Dunne Karin , Wei Andrew H. ,   Australasian Leukaemia and Lymphoma Group (ALLG)
Published: March 2024

Despite an increasing desire to use historical cohorts as “synthetic” controls for new drug evaluation, limited data exist regarding the comparability of real-world outcomes to those in clinical trials. Governmental cancer data often lacks details on treatment, response, and molecular characterization of disease sub-groups. The Australasian Leukaemia and Lymphoma Group National Blood Cancer Registry (ALLG NBCR) includes source information on morphology, cytogenetics, flow cytometry, and molecular features linked to treatment received (including transplantation), response to treatment, relapse, and survival outcome. Using data from 942 AML patients enrolled between 2012–2018, we assessed age and disease-matched control and interventional populations from published randomized trials that led to the registration of midostaurin, gemtuzumab ozogamicin, CPX-351, oral azacitidine, and venetoclax. Our analyses highlight important differences in real-world outcomes compared to clinical trial populations, including variations in anthracycline type, cytarabine intensity and scheduling during consolidation, and the frequency of allogeneic hematopoietic cell transplantation in first remission. Although real-world outcomes were comparable to some published studies, notable differences were apparent in others. If historical datasets were used to assess the impact of novel therapies, this work underscores the need to assess diverse datasets to enable geographic differences in treatment outcomes to be accounted for.
Fast and flexible profiling of chromatin accessibility and total RNA expression in single nuclei using Microwell-seq3
Authors: Ye Fang , Zhang Shuang , Fu Yuting , Yang Lei , Zhang Guodong , Wu Yijun , Pan Jun , Chen Haide , Wang Xinru , Ma Lifeng , Niu Haofu , Jiang Mengmeng , Zhang Tingyue , Jia Danmei , Wang Jingjing , Wang Yongcheng , Han Xiaoping , Guo Guoji
Published: March 2024

Single cell chromatin accessibility profiling and transcriptome sequencing are the most widely used technologies for single-cell genomics. Here, we present Microwell-seq3, a high-throughput and facile platform for high-sensitivity single-nucleus chromatin accessibility or full-length transcriptome profiling. The method combines a preindexing strategy and a penetrable chip-in-a-tube for single nucleus loading and DNA amplification and therefore does not require specialized equipment. We used Microwell-seq3 to profile chromatin accessibility in more than 200,000 single nuclei and the full-length transcriptome in ~50,000 nuclei from multiple adult mouse tissues. Compared with the existing polyadenylated transcript capture methods, integrative analysis of cell type-specific regulatory elements and total RNA expression uncovered comprehensive cell type heterogeneity in the brain. Gene regulatory networks based on chromatin accessibility profiling provided an improved cell type communication model. Finally, we demonstrated that Microwell-seq3 can identify malignant cells and their specific regulons in spontaneous lung tumors of aged mice. We envision a broad application of Microwell-seq3 in many areas of research.
Ecological countermeasures to prevent pathogen spillover and subsequent pandemics
Authors: Plowright Raina K. , Ahmed Aliyu N. , Coulson Tim , Crowther Thomas W. , Ejotre Imran , Faust Christina L. , Frick Winifred F. , Hudson Peter J. , Kingston Tigga , Nameer P. O. , O’Mara M. Teague , Peel Alison J. , Possingham Hugh , Razgour Orly , Reeder DeeAnn M. , Ruiz-Aravena Manuel , Simmons Nancy B. , Srinivas Prashanth N. , Tabor Gary M. , Tanshi Iroro , Thompson Ian G. , Vanak Abi T. , Vora Neil M. , Willison Charley E. , Keeley Annika T. H.
Published: March 2024

Substantial global attention is focused on how to reduce the risk of future pandemics. Reducing this risk requires investment in prevention, preparedness, and response. Although preparedness and response have received significant focus, prevention, especially the prevention of zoonotic spillover, remains largely absent from global conversations. This oversight is due in part to the lack of a clear definition of prevention and lack of guidance on how to achieve it. To address this gap, we elucidate the mechanisms linking environmental change and zoonotic spillover using spillover of viruses from bats as a case study. We identify ecological interventions that can disrupt these spillover mechanisms and propose policy frameworks for their implementation. Recognizing that pandemics originate in ecological systems, we advocate for integrating ecological approaches alongside biomedical approaches in a comprehensive and balanced pandemic prevention strategy.
Predicting and improving complex beer flavor through machine learning
Authors: Schreurs Michiel , Piampongsant Supinya , Roncoroni Miguel , Cool Lloyd , Herrera-Malaver Beatriz , Vanderaa Christophe , Theßeling Florian A. , Kreft Łukasz , Botzki Alexander , Malcorps Philippe , Daenen Luk , Wenseleers Tom , Verstrepen Kevin J.
Published: March 2024

The perception and appreciation of food flavor depends on many interacting chemical compounds and external factors, and therefore proves challenging to understand and predict. Here, we combine extensive chemical and sensory analyses of 250 different beers to train machine learning models that allow predicting flavor and consumer appreciation. For each beer, we measure over 200 chemical properties, perform quantitative descriptive sensory analysis with a trained tasting panel and map data from over 180,000 consumer reviews to train 10 different machine learning models. The best-performing algorithm, Gradient Boosting, yields models that significantly outperform predictions based on conventional statistics and accurately predict complex food features and consumer appreciation from chemical profiles. Model dissection allows identifying specific and unexpected compounds as drivers of beer flavor and appreciation. Adding these compounds results in variants of commercial alcoholic and non-alcoholic beers with improved consumer appreciation. Together, our study reveals how big data and machine learning uncover complex links between food chemistry, flavor and consumer perception, and lays the foundation to develop novel, tailored foods with superior flavors.
Enantioselective total synthesis of (‒)-lucidumone enabled by tandem prins cyclization/cycloetherification sequence
Authors: Liao Xian-Zhang , Wang Ran , Wang Xin , Li Guang
Published: March 2024

The Ganoderma meroterpenoids are a growing class of natural products with architectural complexity, and exhibit a wide range of biological activities. Here, we report an enantioselective total synthesis of the Ganoderma meroterpenoid (‒)-lucidumone. The synthetic route features several key transformations, including a) a Cu-catalyzed enantioselective silicon-tethered intramolecular Diels-Alder cycloaddition to construct the highly functionalized bicyclo[2.2.2]octane moiety; b) Brønsted acid promoted tandem O-deprotection/Prins cyclization/Cycloetherification sequence followed by oxidation to install concurrently the tetrahydrofuran and the fused indanone framework; c) Fleming-Tamao oxidation to generate the secondary hydroxyl; d) an iron-catalyzed Wacker-type oxidation of hindered vinyl group to methyl ketone.
Synergistic morphology and feedback control for traversal of unknown compliant obstacles with aerial robots
Authors: Aucone Emanuele , Geckeler Christian , Morra Daniele , Pallottino Lucia , Mintchev Stefano
Published: March 2024

Animals traverse vegetation by direct physical interaction using their entire body to push aside and slide along compliant obstacles. Current drones lack this interaction versatility that stems from synergies between body morphology and feedback control modulated by sensing. Taking inspiration from nature, we show that a task-oriented design allows a drone with a minimalistic controller to traverse obstacles with unknown elastic responses. A discoid sensorized shell allows to establish and sense contacts anywhere along the shell and facilitates sliding along obstacles. This simplifies the formalization of the control strategy, which does not require a model of the interaction with the environment, nor high-level switching conditions for alternating between pushing and sliding. We utilize an optimization-based controller that ensures safety constraints on the robot’s state and dampens the oscillations of the environment during interaction, even if the elastic response is unknown and variable. Experimental evaluation, using a hinged surface with three different stiffness values ranging from 18 to 155.5 N mm rad−1, validates the proposed embodied aerial physical interaction strategy. By also showcasing the traversal of isolated branches, this work makes an initial contribution toward enabling drone flight across cluttered vegetation, with potential applications in environmental monitoring, precision agriculture, and search and rescue.
Spatial transcriptomics reveals molecular dysfunction associated with cortical Lewy pathology
Authors: Goralski Thomas M. , Meyerdirk Lindsay , Breton Libby , Brasseur Laura , Kurgat Kevin , DeWeerd Daniella , Turner Lisa , Becker Katelyn , Adams Marie , Newhouse Daniel J. , Henderson Michael X.
Published: March 2024

A key hallmark of Parkinson’s disease (PD) is Lewy pathology. Composed of α-synuclein, Lewy pathology is found both in dopaminergic neurons that modulate motor function, and cortical regions that control cognitive function. Recent work has established the molecular identity of dopaminergic neurons susceptible to death, but little is known about cortical neurons susceptible to Lewy pathology or molecular changes induced by aggregates. In the current study, we use spatial transcriptomics to capture whole transcriptome signatures from cortical neurons with α-synuclein pathology compared to neurons without pathology. We find, both in PD and related PD dementia, dementia with Lewy bodies and in the pre-formed fibril α-synucleinopathy mouse model, that specific classes of excitatory neurons are vulnerable to developing Lewy pathology. Further, we identify conserved gene expression changes in aggregate-bearing neurons that we designate the Lewy-associated molecular dysfunction from aggregates (LAMDA) signature. Neurons with aggregates downregulate synaptic, mitochondrial, ubiquitin-proteasome, endo-lysosomal, and cytoskeletal genes and upregulate DNA repair and complement/cytokine genes. Our results identify neurons vulnerable to Lewy pathology in the PD cortex and describe a conserved signature of molecular dysfunction in both mice and humans.
Electricity generation from carbon dioxide adsorption by spatially nanoconfined ion separation
Authors: Wang Zhuyuan , Hu Ting , Tebyetekerwa Mike , Zeng Xiangkang , Du Fan , Kang Yuan , Li Xuefeng , Zhang Hao , Wang Huanting , Zhang Xiwang
Published: March 2024

Selective ion transport underpins fundamental biological processes for efficient energy conversion and signal propagation. Mimicking these ‘ionics’ in synthetic nanofluidic channels has been increasingly promising for realizing self-sustained systems by harvesting clean energy from diverse environments, such as light, moisture, salinity gradient, etc. Here, we report a spatially nanoconfined ion separation strategy that enables harvesting electricity from CO2 adsorption. This breakthrough relies on the development of Nanosheet-Agarose Hydrogel (NAH) composite-based generators, wherein the oppositely charged ions are released in water-filled hydrogel channels upon adsorbing CO2. By tuning the ion size and ion-channel interactions, the released cations at the hundred-nanometer scale are spatially confined within the hydrogel network, while ångström-scale anions pass through unhindered. This leads to near-perfect anion/cation separation across the generator with a selectivity (D-/D+) of up to 1.8 × 106, allowing conversion into external electricity. With amplification by connecting multiple as-designed generators, the ion separation-induced electricity reaching 5 V is used to power electronic devices. This study introduces an effective spatial nanoconfinement strategy for widely demanded high-precision ion separation, encouraging a carbon-negative technique with simultaneous CO2 adsorption and energy generation.
Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome
Authors: Meester Josephina A. N. , Hebert Anne , Bastiaansen Maaike , Rabaut Laura , Bastianen Jarl , Boeckx Nele , Ashcroft Kathryn , Atwal Paldeep S. , Benichou Antoine , Billon Clarisse , Blankensteijn Jan D. , Brennan Paul , Bucks Stephanie A. , Campbell Ian M. , Conrad Solène , Curtis Stephanie L. , Dasouki Majed , Dent Carolyn L. , Eden James , Goel Himanshu , Hartill Verity , Houweling Arjan C. , Isidor Bertrand , Jackson Nicola , Koopman Pieter , Korpioja Anita , Kraatari-Tiri Minna , Kuulavainen Liina , Lee Kelvin , Low Karen J. , Lu Alan C. , McManus Morgan L. , Oakley Stephen P. , Oliver James , Organ Nicole M. , Overwater Eline , Revencu Nicole , Trainer Alison H. , Trivedi Bhavya , Turner Claire L. S. , Whittington Rebecca , Zankl Andreas , Zentner Dominica , Van Laer Lut , Verstraeten Aline , Loeys Bart L.
Published: March 2024

Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females). The identified BGN variants were shown to lead to loss-of-function by cDNA and Western Blot analyses of skin fibroblasts or were strongly predicted to lead to loss-of-function based on the nature of the variant. No (likely) pathogenic missense variants without additional (predicted) splice effects were identified. Interestingly, a male proband with a deletion spanning the coding sequence of BGN and the 5’ untranslated region of the downstream gene (ATP2B3) presented with a more severe skeletal phenotype. This may possibly be explained by expressional activation of the downstream ATPase ATP2B3 (normally repressed in skin fibroblasts) driven by the remnant BGN promotor. This study highlights that aneurysms and dissections in MRLS extend beyond the thoracic aorta, affecting the entire arterial tree, and cardiovascular symptoms may coincide with non-specific connective tissue features. Furthermore, the clinical presentation is more severe and penetrant in males compared to females. Extensive analysis at RNA, cDNA, and/or protein level is recommended to prove a loss-of-function effect before determining the pathogenicity of identified BGN missense and non-canonical splice variants. In conclusion, distinct mechanisms may underlie the wide phenotypic spectrum of MRLS patients carrying loss-of-function variants in BGN.
A near-complete genome assembly of Monochamus alternatus a major vector beetle of pinewood nematode
Authors: Xing Longsheng , Liu Bo , Yu Dunyang , Tang Xuan , Sun Jianghua , Zhang Bin
Published: March 2024

The Japanese sawyer beetle, Monochamus alternatus, is not only one of the most important wood boring pest itself, but also a major vector of the invasive pinewood nematode (PWN), which is the causal agent of the devastative pine wilt disease (PWD) and threats the global pine forest. Here, we present a near-complete genome of M. alternatus at the chromosome level. The assembled genome was 792.05 Mb with contig N50 length of 55.99 Mb, which is the largest N50 size among the sequenced Coleoptera insects currently. 99.57% of sequence was anchored onto ten pseudochromosomes (one X-chromosome and nine autosomes), and the final genome harbored only 13 gaps. BUSCO evaluation revealed the presence of 99.0% of complete core genes. Thus, our genome assembly represented the highest-contiguity genome assembly as well as high completeness in insects so far. We identified 20,471 protein-coding genes, of which 20,070 (98.04%) were functionally annotated. The genome assembly of M. alternatus provides a valuable resource for exploring the evolution of the symbiosis between PWN and the vector insects.
Comparative evaluation of non-invasive tests for risk stratification for cause specific mortality in at-risk population of hepatic fibrosis
Authors: Park Huiyul , Yoon Eileen L. , Kim Mimi , Kim Hye-Lin , Kim Mi Kyung , Kim Yu-Mi , Jun Dae Won
Published: March 2024

Our study aimed to conduct a comparative evaluation of various noninvasive tests (NITs) for risk stratification in at-risk population for non-alcoholic fatty liver disease (NAFLD), focusing on cardiovascular and liver-related mortality. A total of 21,715 adults aged 40 years and older were enrolled at baseline. The mean follow-up period was 12.39 years. Three types of NITs (fibrosis-4 index [FIB-4], NAFLD fibrosis score [NFS], and steatosis-associated fibrosis estimator [SAFE] score) were used. When using the low cut-off as a 'rule-out' strategy, there were no significant differences in cardiovascular mortality between the 'rule-out' (low-risk) group and the 'rule-in' (intermediate- or high-risk) group based on FIB-4 (aHR = 1.029, P = 0.845) or NFS (aHR = 0.839, P = 0.271) classification. However, the SAFE score exhibited higher sensitivity in predicting cardiovascular mortality compared to FIB-4 or NFS (73.3% in SAFE score vs. 29.6% in FIB-4 or 21.3% in NFS). Only the SAFE score could effectively differentiate the risk between low- and intermediate- or high-risk groups for all types of mortality (all P values for aHR < 0.001). The low cutoff value of the SAFE score discriminated not only liver-related mortality but also identified the cardiovascular high-risk group in the community cohort.
Antimicrobial resistance burden pre and post-COVID-19 pandemic with mapping the multidrug resistance in Egypt: a comparative cross-sectional study
Authors: Abdelaziz Abdelmoneim Shaimaa , Mohamed Ghazy Ramy , Anwar Sultan Eman , Hassaan Mahmoud A. , Anwar Mahgoub Mohamed
Published: March 2024

Overuse of antibiotics during coronavirus disease 2019 (COVID-19) in an attempt to reduce COVID-19 mortality in the short term may have contributed to long-term mortality from antimicrobial resistance (AMR). The aim of this study was to evaluate the impact of the COVID-19 pandemic on AMR in Egypt and map the distribution of multidrug-resistant (MDR) and extensive drug-resistant (XDR) across Egypt. Through a multicenter cross-sectional study 2430 culture results were collected in 2019 and 2022 pre and post-COVID-19 pandemic in Egypt, including 400 Klebsiella pneumoniae, 760 Escherichia coli, 650 Acinetobacter baumannii, and 620 Methicillin-resistantstaphylococcus aureus (MRSA) culture results. MDR and XDR culture results distribution across Egypt was highlighted through the geographic information system. Mixed effect logistic regression models and sub-group analysis were performed according to the type of specimens to test the impact of COVID-19 on resistance. Adjusted analysis demonstrated K. pneumoniae resistance has increased against quinolones and carbapenems (P < 0.001). Resistance of E. coli has increased significantly against imipenem and meropenem. While E.coli susceptibility has increased to cefoxitin, levofloxacin, and ciprofloxacin. A. baumannii resistance has increased more than double against ceftazidime, cefepime, and piperacillin-tazobactam (P < 0.001). MRSA reserved its susceptibility to vancomycin and linezolid. MDR K. pneumoniae and A. baumannii have increased post-COVID-19 from 67% to 94% and from 79% to 98%, respectively (P < 0.001). XDR K. pneumoniae and A. baumannii have increased from 6% to 46%, and from 47% to 69%, respectively (P < 0.001). COVID-19 has changed the profile of AMR in Egypt so that urgent action is required to mitigate this threat and preserve our capacity to face infections in future decades.
Cancer incidence trends in New York State and associations with common population-level exposures 2010–2018: an ecological study
Authors: Yuan Haokun , Kehm Rebecca D. , Daaboul Josephine M. , Lloyd Susan E. , McDonald Jasmine A. , Mu Lina , Tehranifar Parisa , Zhang Kai , Terry Mary Beth , Yang Wan
Published: March 2024

The impact of common environmental exposures in combinations with socioeconomic and lifestyle factors on cancer development, particularly for young adults, remains understudied. Here, we leveraged environmental and cancer incidence data collected in New York State at the county level to examine the association between 31 exposures and 10 common cancers (i.e., lung and bronchus, thyroid, colorectal, kidney and renal pelvis, melanoma, non-Hodgkin lymphoma, and leukemia for both sexes; corpus uteri and female breast cancer; prostate cancer), for three age groups (25–49, 50–69, and 70–84 year-olds). For each cancer, we stratified by age group and sex, and applied regression models to examine the associations with multiple exposures simultaneously. The models included 642,013 incident cancer cases during 2010–2018 and found risk factors consistent with previous reports (e.g., smoking and physical inactivity). Models also found positive associations between ambient air pollutants (ozone and PM2.5) and prostate cancer, female breast cancer, and melanoma of the skin across multiple population strata. Additionally, the models were able to better explain the variation in cancer incidence data among 25–49 year-olds than the two older age groups. These findings support the impact of common environmental exposures on cancer development, particularly for younger age groups.
Timing and impact of percutaneous endoscopic gastrostomy insertion in patients with amyotrophic lateral sclerosis: a comprehensive analysis
Authors: Son Bugyeong , Lee Jisu , Ryu Soorack , Park Yongsoon , Kim Seung Hyun
Published: March 2024

Dysphagia is common in amyotrophic lateral sclerosis (ALS) patients, often requiring percutaneous endoscopic gastrostomy (PEG) for enteral nutrition. We retrospectively analyzed data from 188 Korean patients with ALS who underwent PEG tube insertion at five-time points: symptom onset (t1), diagnosis (t2), recommended time for gastrostomy (t3), PEG insertion (t4), and one-year post-insertion (t5). The recommended time point for gastrostomy (T-rec for gastrostomy) was defined as the earlier time point between a weight loss of more than 10% and advanced dysphagia indicated by the ALSFRS-R swallowing subscore of 2 or less. The T-rec for gastrostomy was reached at 22 months after symptom onset, followed by PEG insertion at 30 months, resulting in an 8-month delay. During the delay, the ALSFRS-R declined most rapidly at 1.7 points/month, compared to 0.8 points/month from symptom onset to diagnosis, 0.7 points/month from diagnosis to T-rec for gastrostomy, and 0.6 points/month after the PEG insertion. It is crucial to discuss PEG insertion before significant weight loss or severe dysphagia occurs and minimize the delay between the recommended time for gastrostomy and the actual PEG insertion. A stratified and individualized multidisciplinary team approach with careful symptom monitoring and proactive management plans, including early PEG insertion, should be prioritized to improve patient outcomes.
GeneAI 3.0: powerful, novel, generalized hybrid and ensemble deep learning frameworks for miRNA species classification of stationary patterns from nucleotides
Authors: Singh Jaskaran , Khanna Narendra N. , Rout Ranjeet K. , Singh Narpinder , Laird John R. , Singh Inder M. , Kalra Mannudeep K. , Mantella Laura E. , Johri Amer M. , Isenovic Esma R. , Fouda Mostafa M. , Saba Luca , Fatemi Mostafa , Suri Jasjit S.
Published: March 2024

Due to the intricate relationship between the small non-coding ribonucleic acid (miRNA) sequences, the classification of miRNA species, namely Human, Gorilla, Rat, and Mouse is challenging. Previous methods are not robust and accurate. In this study, we present AtheroPoint’s GeneAI 3.0, a powerful, novel, and generalized method for extracting features from the fixed patterns of purines and pyrimidines in each miRNA sequence in ensemble paradigms in machine learning (EML) and convolutional neural network (CNN)-based deep learning (EDL) frameworks. GeneAI 3.0 utilized fiveconventional(Entropy, Dissimilarity, Energy, Homogeneity, and Contrast), and threecontemporary(Shannon entropy, Hurst exponent, Fractal dimension) features, to generate acompositefeature set from given miRNA sequences which were then passed into our ML and DL classification framework. A set of 11 new classifiers was designed consisting of 5 EML and 6 EDL for binary/multiclass classification. It was benchmarked against 9 solo ML (SML), 6 solo DL (SDL), 12 hybrid DL (HDL) models, resulting in a total of 11 + 27 = 38 models were designed. Four hypotheses were formulated and validated using explainable AI (XAI) as well as reliability/statistical tests. The order of the mean performance using accuracy (ACC)/area-under-the-curve (AUC) of the 24 DL classifiers was: EDL > HDL > SDL. The mean performance of EDL models with CNN layers was superior to that without CNN layers by 0.73%/0.92%. Mean performance of EML models was superior to SML models with improvements of ACC/AUC by 6.24%/6.46%. EDL models performed significantly better than EML models, with a mean increase in ACC/AUC of 7.09%/6.96%. The GeneAI 3.0 tool produced expected XAI feature plots, and the statistical tests showed significantp-values. Ensemble models with composite features are highly effective and generalized models for effectively classifying miRNA sequences.
Impacts of cobalt and zinc on improving peanuts nutrient uptake, yield and irrigation water use efficiency under different irrigation levels
Authors: Elshamly Ayman M. S. , Nassar Saad M. A.
Published: March 2024

The knowledge of proper fertigation across various irrigation levels is necessary for maximizing peanut yield and irrigation use efficiency in arid areas, and it also can effectively alleviate the risk of nutrient deficiency induced by water stress. This study evaluated the effectiveness of cobalt combined with two zinc application methods on peanut nutrient uptake, yield, and irrigation water use efficiency across varying irrigation levels. A split-split plot experiment was carried out in 2021 and 2022. Three peanut gross water requirement (GWR) levels (100%, 80%, and 60%) were designated for main plots. Subplots featured plants treated with either 0 or 7.5 mg L−1 of cobalt. The sub-sub plots assessed chelated zinc effects at rates of 0 and 2 g L−1 via foliar and soil applications. In comparison to the control (100% GWR), nutrient uptake decreased, with sodium being the exception, and there was an increase in soil pH at 60% GWR. The results showed also significant reductions in yield and water use by approximately 60.3% and 38.1%, respectively. At this irrigation level, applying zinc via soil, either alone or combined with cobalt, led to significant yield increases of 89.7% and 191.3% relative to the control. Also, it’s crucial to note that cobalt application negatively affected iron and copper at 60% GWR, but this impact was lessened with soil-applied zinc. Hence, under a similar circumstance, treating stressed peanut plants with additional foliar applications of iron + copper and applying zinc via soil, could enhance nutrient uptake and improve yield. On the other hand, at 80% GWR, a combination of foliar-applied zinc and cobalt, had a tremendous impact on the absorption of (nitrogen, phosphorus, magnesium, and zinc), resulting in enhanced agronomic traits and decreased water losses. Additionally, at this irrigation level, foliar zinc application alone yielded a 32.4% increase compared to the 80% GWR control. When combined with cobalt, there was a 70.0% surge in water use. Based on this knowledge, the study suggests using 80% GWR and treating peanut plants with a combination of foliar-applied zinc and cobalt. This strategy aids plants in countering the adverse effects of water stress, ultimately leading to enhanced yield and irrigation water use efficiency.