bluuebunny/crossref_metadata_2025 huggingface dataset:
“Helping Mentally Ill, a Reward Both in this Life and After”: A Qualitative Study Among Community Health Professionals in Somaliland
Authors: Nyassi Sungkutu , Abdi Yakoub Aden , Minto John , Osman Fatumo
Published: January 2023

This study aimed to describe the experiences of community mental health workers, predominantly female, nurses and doctors providing community-based mental health services in Borama, Somaliland. A qualitative explorative study using focus group discussions was conducted. Data were collected from three focus group discussions with 22 female community health workers, two medical doctors, and two registered nurses and analyzed using content analysis with an inductive approach. Three main categories were identified from the analysis: (1) bridging the mental health gap in the community; (2) working in a constrained situation; and (3) being altruistic. Overall, the community mental health workers felt that their role was to bridge the mental health gap in the community. They described their work as a rewarding and motivated them to continue despite challenges and improving community healthcare workers’ work conditions and providing resources in mental health services will contribute to strengthening mental health services in Somaliland.
Detection of Delaminations in Concrete Plates Using a Laser Ablation Impact Echo Technique
Authors: Scherr Johannes F. , Kollofrath Jochen , Popovics John S. , Bühling Benjamin , Grosse Christian U.
Published: January 2023

This study investigates the non-destructive detection of delaminations in concrete plates using non-contact laser ablation, instead of the conventional hammer excitation, as part of the impact echo method. We performed tests on five concrete specimens of different sizes, two of which contained artificial delaminations. A range of steel ball hammers was used as reference impulse sources, the responses of which were compared with wave excitation generated by a 7 ns pulsed 1064 nm Nd:YAG laser with 150 mJ pulse energy. Signals were recorded by surface-mounted accelerometers and two contactless methods: microphones and a laser Doppler vibrometer. The laser generates frequencies across a broad range of frequencies (0 to 150 kHz) but with much less energy than the hammers' narrower frequency spectra; the laser pulse energy transferred into the specimen is 0.07 mJ, corresponding to about 0.5 ‰ of the impulse source energy. Because of this, the thick intact plates' characteristic thickness stretch resonance frequency can be reliably detected by the hammer excitations but not when using laser excitation. However, the laser can excite low-frequency flexural vibration modes over a shallow delamination at 3 cm depth. The low-frequency flexural vibration results are verified by numerical natural frequency analysis.
How pervasive is corporate fraud?
Authors: Dyck Alexander , Morse Adair , Zingales Luigi
Published: January 2023

We provide a lower-bound estimate of the undetected share of corporate fraud. To identify the hidden part of the “iceberg,” we exploit Arthur Andersen’s demise, which triggered added scrutiny on Arthur Andersen’s former clients and thereby increased the detection likelihood of preexisting frauds. Our evidence suggests that in normal times only one-third of corporate frauds are detected. We estimate that on average 10% of large publicly traded firms are committing securities fraud every year, with a 95% confidence interval of 7%-14%. Combining fraud pervasiveness with existing estimates of the costs of detected and undetected fraud, we estimate that corporate fraud destroys 1.6% of equity value each year, equal to $830 billion in 2021.
Surface Plasmon Resonance Based Sensor for Amaranth Detection With Molecularly Imprinted Nanoparticles
Authors: Ozgur Fatma Ozge , Çimen Duygu , Denizli Adil , Bereli Nilay
Published: January 2023

Amaranth imprinted nanoparticles were prepared by two-phase mini emulsion polymerization of hydroxyethyl methacrylate and ethylene glycol dimethacrylate using acrylamide and methacrylic acid as functional monomers. The amaranth non-imprinted nanoparticle was prepared with the same procedure without using amaranth. Amaranth imprinted and non-imprinted nanoparticles were attached on the chip surface modified with allyl mercaptan. The surfaces of the surface plasmon resonance (SPR) sensor were characterized by the ellipsometry, contact angle, and atomic force microscopy. Amaranth solutions with different concentrations (0.1mg/mL–150mg/mL) were prepared with the pH 7.4 phosphate buffer. The limit of detection and limit of quantification were 0.0180mg/mL and 0.06mg/mL, respectively. When the selectivity of the amaranth imprinted SPR sensor was compared with the competing molecules tartrazine and allura red, it was observed that the target molecule amaranth was 5.64 times and 5.18 times more selective than allura red and tartrazine, respectively. The liquid chromatography-mass spectrometry technique (LC-MS) was used for validation studies. According to the results obtained from both SPR sensor and LC-MS analyses, the amaranth recovery (%) from fruit juices was observed between 96% and 99%.
Modules and representations up to homotopy of Lie n-algebroids
Authors: Jotz M. , Mehta R. A. , Papantonis T.
Published: January 2023

This paper studies differential graded modules and representations up to homotopy of Lie n-algebroids, for general $$n\in {\mathbb {N}}$$

n
∈
N

. The adjoint and coadjoint modules are described, and the corresponding split versions of the adjoint and coadjoint representations up to homotopy are explained. In particular, the case of Lie 2-algebroids is analysed in detail. The compatibility of a Poisson bracket with the homological vector field of a Lie n-algebroid is shown to be equivalent to a morphism from the coadjoint module to the adjoint module, leading to an alternative characterisation of non-degeneracy of higher Poisson structures. Moreover, the Weil algebra of a Lie n-algebroid is computed explicitly in terms of splittings, and representations up to homotopy of Lie n-algebroids are used to encode decomposed VB-Lie n-algebroid structures on double vector bundles.
Antifungal antibodies present in intravenous immunoglobulin derived from China
Authors: Wang Yanfang , Liu Yugu , Jiang Susu , Zhao Yan , Cai Jianpiao , Hao Wei , Fu Ning
Published: January 2023

Fungal infections usually occur in immunocompromised patients. Intravenous immunoglobulin (IVIG) has been used as therapeutic interventions for many infectious diseases, but seldom applied in mycosis due to unknown antifungal specificity. This study aims to determine the presence of antifungal antibodies in IVIG. Binding reactivity of IVIG with crude and recombinant antigens of Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans and Talaromyces marneffei were observed in a dose-dependent manner, similar with mixed normal human sera. The antifungal specificity was further confirmed by competitive enzyme-linked immunosorbent assays (ELISA) inhibited by rabbit specific antifungal polyclonal antibodies (PAbs) and homogenous crude antigens with inhibitions of 65.5-87.2% and 73.1-94.2%, respectively. Moreover, IVIG also reacted with fungal glycoproteins (Csa2, Cpl1 and Mp1p) in a dose-dependent way, which was inhibited by specific rabbit PAbs and homogenous antigens with different inhibitions and pulled down 72.8-83.8% of specific antibodies if preabsorption IVIG with Dynabeads® coupled with homogenous glycoproteins. These results furthermore verified the antifungal specificity of IVIG. Among four brands of IVIG, there was different antifungal IgG against C. albicans (P < 0.05) and C. neoformans (P < 0.05), while no difference for A. fumigatus (P = 0.086) and T. marneffei (P = 0.057). IVIG contained a significantly higher level of specific IgG for C. albicans than other three fungi (P <0.001). In conclusion, we proved antifungal IgG against C. albicans, A. fumigatus, C. neoformans and T. marneffei present in IVIG, which might be expected to provide a possible immunoregulation choice for mycosis and an evaluation to humoral immunity against fungi.
Parker and Evans's Inside Lawyers' Ethics
Authors: Holmes Vivien , Bartlett Francesca
Published: January 2023

Parker and Evans's Inside Lawyers' Ethics provides a practical and engaging introduction to ethical decision-making in legal practice in Australia. Underpinned by four theoretical concepts – adversarial advocacy, responsible lawyering, moral activism and ethics of care – this text analyses legal and professional frameworks, highlighting relevant parts of the Australian Solicitors' Conduct Rules. Case studies and discussion questions offer contemporary, practical examples of the application of ethics. The book also addresses the challenge of ethical action and offers techniques to deal with ethical conflicts.This edition has been comprehensively updated and discusses the implications of advances in legal technology, mental ill-health in the profession and the complexities of government legal practice. A new chapter covers lawyers' ethical obligation to address the legal challenges posed by climate change. Written by an expert author team, Parker and Evans's Inside Lawyers' Ethics empowers readers to identify ethical challenges and resolve them through good decision-making practices.
Syntomic complexes and p-adic étale Tate twists
Authors: Bhatt Bhargav , Mathew Akhil
Published: January 2023

The primary goal of this paper is to identify syntomic complexes with the p-adic étale Tate twists of Geisser–Sato–Schneider on regular p-torsion-free schemes. Our methods apply naturally to a broader class of schemes that we call ‘F-smooth’. The F-smoothness of regular schemes leads to new results on the absolute prismatic cohomology of regular schemes.
Cerebral blood flow changes and their genetic mechanisms in major depressive disorder: a combined neuroimaging and transcriptome study
Authors: Sun Xuetian , Huang Weisheng , Wang Jie , Xu Ruoxuan , Zhang Xiaohan , Zhou Jianhui , Zhu Jiajia , Qian Yinfeng
Published: January 2023

Background

Extensive research has shown abnormal cerebral blood flow (CBF) in patients with major depressive disorder (MDD) that is a heritable disease. The objective of this study was to investigate the genetic mechanisms of CBF abnormalities in MDD.

Methods

To achieve a more thorough characterization of CBF changes in MDD, we performed a comprehensive neuroimaging meta-analysis of previous literature as well as examined group CBF differences in an independent sample of 133 MDD patients and 133 controls. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging spatial association analyses were conducted to identify genes whose expression correlated with CBF changes in MDD, followed by a set of gene functional feature analyses.

Results

We found increased CBF in the reward circuitry and default-mode network and decreased CBF in the visual system in MDD patients. Moreover, these CBF changes were spatially associated with expression of 1532 genes, which were enriched for important molecular functions, biological processes, and cellular components of the cerebral cortex as well as several common mental disorders. Concurrently, these genes were specifically expressed in the brain tissue, in immune cells and neurons, and during nearly all developmental stages. Regarding behavioral relevance, these genes were associated with domains involving emotion and sensation. In addition, these genes could construct a protein-protein interaction network supported by 60 putative hub genes with functional significance.

Conclusions

Our findings suggest a cerebral perfusion redistribution in MDD, which may be a consequence of complex interactions of a wide range of genes with diverse functional features.
Alternative metrics for characterizing longer-term clinical outcomes in difficult-to-treat depression: I. Association with change in quality of life
Authors: Sackeim Harold A. , Rush A. John , Greco Teresa , Jiang Mei , Badejo Sarah , Bunker Mark T. , Aaronson Scott T. , Conway Charles R. , Demyttenaere Koen , Young Allan H. , McAllister-Williams R. Hamish
Published: January 2023

Background

In difficult-to-treat depression (DTD) the outcome metrics historically used to evaluate treatment effectiveness may be suboptimal. Metrics based on remission status and on single end-point (SEP) assessment may be problematic given infrequent symptom remission, temporal instability, and poor durability of benefit in DTD.

Methods

Self-report and clinician assessment of depression symptom severity were regularly obtained over a 2-year period in a chronic and highly treatment-resistant registry sample (N = 406) receiving treatment as usual, with or without vagus nerve stimulation. Twenty alternative metrics for characterizing symptomatic improvement were evaluated, contrasting SEP metrics with integrative (INT) metrics that aggregated information over time. Metrics were compared in effect size and discriminating power when contrasting groups that did (N = 153) and did not (N = 253) achieve a threshold level of improvement in end-point quality-of-life (QoL) scores, and in their association with continuous QoL scores.

Results

Metrics based on remission status had smaller effect size and poorer discrimination of the binary QoL outcome and weaker associations with the continuous end-point QoL scores than metrics based on partial response or response. The metrics with the strongest performance characteristics were the SEP measure of percentage change in symptom severity and the INT metric quantifying the proportion of the observation period in partial response or better. Both metrics contributed independent variance when predicting end-point QoL scores.

Conclusions

Revision is needed in the metrics used to quantify symptomatic change in DTD with consideration of INT time-based measures as primary or secondary outcomes. Metrics based on remission status may not be useful.
Solving two-dimensional H(curl)-elliptic interface systems with optimal convergence on unfitted meshes
Authors: Guo Ruchi , Lin Yanping , Zou Jun
Published: January 2023

Finite element methods developed for unfitted meshes have been widely applied to various interface problems. However, many of them resort to non-conforming spaces for approximation, which is a critical obstacle for the extension to
$\textbf{H}(\text{curl})$
equations. This essential issue stems from the underlying Sobolev space
$\textbf{H}^s(\text{curl};\,\Omega)$
, and even the widely used penalty methodology may not yield the optimal convergence rate. One promising approach to circumvent this issue is to use a conforming test function space, which motivates us to develop a Petrov–Galerkin immersed finite element (PG-IFE) method for
$\textbf{H}(\text{curl})$
-elliptic interface problems. We establish the Nédélec-type IFE spaces and develop some important properties including their edge degrees of freedom, an exact sequence relating to the
$H^1$
IFE space and optimal approximation capabilities. We analyse the inf-sup condition under certain assumptions and show the optimal convergence rate, which is also validated by numerical experiments.
A rare complication after an interventional procedure using the common carotid: carotid pseudoaneurysm in an infant
Authors: Kızılkaya Mete Han , Biçer Mehmet , Ödemiş Ender , Gündoğmuş Cemal Aydın
Published: January 2023

The carotid artery is a valuable vascular access that can be used in patients who have undergone repetitive interventional and surgical procedures and premature babies. In the past, cut-down was used but nowadays, mostly the procedure is performed under ultrasonographic guidance. Complications such as bleeding, haematoma, and pseudoaneurysm may occur when the carotid artery is used as a vascular access for the procedures such as aortic balloon valvuloplasty, coarctation balloon angioplasty, or after interventional or surgical treatments to the carotid artery. Although pseudoaneurysm is very rare, prompt diagnosis and accurate treatment planning are life-saving. In this article, the diagnosis and treatment of pseudoaneurysm in the left common carotid after transcatheter coarctation balloon angioplasty in a 6-month-old infant will be presented.
Screening House: film and material representations of the Cold War’s anxieties
Authors: Aedo Sebastián
Published: January 2023

In 1955 Charles and Ray Eames gathered more than three hundred photographs of their Case Study House #8 in the Pacific Palisades to produce the experimental film House: After Five Years of Living. The film is a visual exploration in which craft and found objects contrast with the mass-produced industrial structure of their house, but also a constant tension between the frantic acceleration of its images and moments of slow pace.

Proceeding from a close reading of House: After Five Years of Living, this article analyses its film and editing technique to proposes how domesticity becomes a screen. This means, an ideological surface promoting the cultural, social, and economic changes of the Cold War period, while simultaneously screening out (obscuring) its anxieties, preoccupations, and fears in its mode of visual representation. In the film, the Case study House #8 exposes and covers, promotes and disguises, veiling some preoccupations and motivations while exhibiting an alternative reality.
Tailoring the truth – evidence on parliamentarians’ responsiveness and misinformation toleration from a field experiment
Authors: Diermeier Matthias
Published: January 2023

Populist radical right parties (PRRPs) claim to be particularly responsive to people’s needs and have been identified as a major source of disinformation. The present contribution sets up a field experiment to zoom in on one-to-one communication between voters and their parliamentarians. By drawing on pieces of misinformation that are present among different parties’ supporters, artificial citizen’s requests are sent to all 2503 German federal parliamentarians. In fact, PRRP politicians do not turn out to be more responsive and they are by far more reluctant to reject misinformation. In contrast, parliamentarians of all other parties largely object to misinformation, even if it matches their political positions and is shared by their electorates. In opposition to PRRP politicians who reveal signs of vote-seeking behaviour, established parties’ communication behaviour indicates a high degree of intrinsic motivation.
Exoskeletons: A challenge for development
Authors: Bengler Klaus , Harbauer Christina M. , Fleischer Martin
Published: January 2023

The development of exoskeletons is currently a lengthy process full of challenges. We are proposing a framework to accelerate the process and make the resulting exoskeletons more user-centered. The needed accomplishments in science are described in an effort to lay the foundation for future research projects. Since the early 2000s, exoskeletons have been discussed as an emerging technology in industrial, medical, or military applications. Those systems are designed to support people during manual tasks. At first, those systems lacked broad acceptance. Many models found their niches in ongoing developments and more diverse systems entering the market. There are still applications that are in dire need of such assistance. Due to the lack of experience with body-worn robotics, the development of such systems has been shaped by trial and error. The lack of legacy products results in longer development times. In this paper, a process to generate a framework is presented to display the required research to enable future exoskeleton designers. Owing to their proximity to the user’s body, exoskeletons are highly complex systems that need sophisticated subsystems, such as kinematic, control, interaction design, or actuators, to be accepted by users. Due to the wide variety of fields and high user demands, a synchronized multidisciplinary effort is necessary. To achieve this, a process to develop a modular framework for exoskeleton design is proposed. It focuses on user- and use-case-centered solutions for matching kinematics, actuation, and control. To ensure the usefulness of the framework, an evaluation of the incorporated solutions is required.
What Is the Benefit of Adding Placebo Side-Effect Information to	Positively Framed Patient Leaflets?
Authors: Saadi Amina , Mahmood Asra , Sweeney Jack , Webster Rebecca K.
Published: January 2023

Abstract: Background: Positively framing side-effect risk in patient information leaflets (PILs) can reduce side-effect expectations and resulting nocebo effects (nonspecific medication side effects unrelated to the drug’s pharmacological action). There is scope to educate patients about nocebo effects in PILs to minimize their occurrence further. Aims: To investigate if incorporating information on placebo-reported side effects reduces side-effect expectations compared to a positively framed-only or standard PIL. Methods: Participants ( N = 443) completed an online study and were randomized to read one of three PILs for a hypothetical antibiotic: standard PIL ( n = 140), positively framed PIL ( n = 151), or positively framed PIL with placebo side-effect information ( n = 152). Participants’ side-effect expectations, absolute risk perceptions, and intended adherence were recorded. Results: The standard PIL resulted in significantly higher side-effect expectations compared to the positively framed + placebo side-effect information PIL. Including the placebo side-effect results had no effect on side-effect expectations compared to the positive framing only PIL, however, there was a significant interaction between health literacy and PIL condition on side-effect expectations. Both positively framed PILs produced more accurate risk estimates for the more common side effects. There was no difference in intended adherence between the three PILs. Limitations: Our findings are limited by the highly educated sample and hypothetical context. Conclusions: There was no benefit of adding placebo side-effect information, however alternative ways of explaining nocebo effects in PILs should be explored utilizing clinical contexts and samples with a wider range of participant ages, and health literacy.
Atmospheric River Contributions to Ice Sheet Hydroclimate at the Last Glacial Maximum
Authors: Skinner Christopher B. , Lora Juan M. , Tabor Clay , Zhu Jiang
Published: January 2023

Atmospheric rivers (ARs) are an important driver of surface mass balance over today's Greenland and Antarctic ice sheets. Using paleoclimate simulations with the Community Earth System Model, we find ARs also had a key influence on the extensive ice sheets of the Last Glacial Maximum (LGM). ARs provide up to 53% of total precipitation along the margins of the eastern Laurentide ice sheet and up to 22%–27% of precipitation along the margins of the Patagonian, western Cordilleran, and western Fennoscandian ice sheets. Despite overall cold conditions at the LGM, surface temperatures during AR events are often above freezing, resulting in more rain than snow along ice sheet margins and conditions that promote surface melt. The results suggest ARs may have had an important role in ice sheet growth and melt during previous glacial periods and may have accelerated ice sheet retreat following the LGM.
Role of Land–Atmosphere Interaction in the 2016 Northeast Asia Heat Wave: Impact of Soil Moisture Initialization
Authors: Yoon Donghyuck , Kang Taehun , Cha Dong‐Hyun , Song Chang‐Keun , Lee Myong‐In , Min Ki‐Hong , Kim Joowan , Chun Jong Ahn , Seo Eunkyo
Published: January 2023

The impact of soil moisture initialization on the 2016 Northeast Asian heat wave was explored using the Land Information System (LIS) Weather Research and Forecasting (WRF) model. To obtain advanced soil moisture estimates, various meteorological variables from the Global Data Assimilation System analysis and Integrated Multi‐Satellite Retrievals for Global Precipitation Measurement observation data were used as atmospheric forcings for the offline simulation of the Noah land surface model (Noah‐LSM). Based on the LIS, Soil Moisture Active Passive satellite were assimilated in the Noah LSM simulation. The assimilated soil moisture estimates revealed the drier land surface conditions over Northeast Asia compared with the product from the National Centers for Environmental Prediction Final Analysis (FNL) and were used as the initial condition of the WRF model. The WRF experiment initialized by the assimilated soil moisture product (LIS experiment) exhibited the observed surface air temperature (SAT) and 500 hPa geopotential height (500 GPH) over Northeast Asia compared with the result from the experiment initialized by the FNL (CTL experiment). At Week 1, the LIS experiment simulated warmer SAT than that from the CTL experiment, which was induced by the negative anomaly of latent heat flux over Mongolia. Then, 500 GPH became strong and spatially expanded in response to the thermal low induced by the warmer SAT, and the SAT was further increased during Weeks 2 and 3.
The prevalence and outcomes of frail older adults in clinical trials in multiple myeloma: A systematic review
Authors: Mian Hira , McCurdy Arleigh , Giri Smith , Grant Shakira , Rochwerg Bram , Winks Erica , Rosko Ashley E. , Engelhardt Monika , Pawlyn Charlotte , Cook Gordon , Jackson Graham , Bringhen Sara , Facon Thierry , Larocca Alessandra , Zweegman Sonja , Wildes Tanya M.
Published: January 2023

Multiple myeloma (MM) is an incurable blood cancer that primarily affects older adults. Several frailty tools have been developed to address the heterogeneity of aging in this population. Uptake of these measures has been variable, leading to a gap in knowledge regarding the proportion of enrolled trial participants considered frail and uncertainty in the treatment-related effects and outcomes among this high-risk population. We performed a systematic review of therapeutic interventional MM clinical trials reporting on frailty. We included 43 clinical trials (24 randomized controlled trials and 19 non-randomized trials) which met eligibility criteria. Frailty was increasingly incorporated in studies in more recent years with 41.9% of included studies being reported in the last two years. Commonly used frailty tools included the International Myeloma Working Group (IMWG) frailty index (41.8%), and the simplified frailty score (39.5%). Frailty status was categorized with 3 levels as (frail, intermediate fit, or fit) in 51.2% of the studies and dichotomized (frail, non-frail) in 18.6% of studies. Frailty prevalence greatly varied across trials ranging from 17.2% to 73.6% of the cohort. Of the included studies, 72.0% conducted subgroup analysis (planned or post-hoc) based on frailty status. Most studies demonstrated a consistent benefit of MM interventions among the frail and non-frail populations, however in general, frail patients had worse outcomes compared to the fit. Although frailty is increasingly being incorporated in MM clinical trials, due to the variation in both the definition and categorization of frailty, there remains heterogeneity in the prevalence of frailty and its potential associated impact on outcomes.
An entosis-like process induces mitotic disruption in Pals1 microcephaly pathogenesis
Authors: Sterling Noelle A. , Park Jun Young , Park Raehee , Cho Seo-Hee , Kim Seonhee
Published: January 2023

Entosis is cell cannibalism utilized by tumor cells to engulf live neighboring cells for pro- or anti-tumorigenic purposes. It is unknown whether this extraordinary cellular event can be pathogenic in other diseases such as microcephaly, a condition characterized by a smaller than normal brain at birth. We find that mice mutant for the human microcephaly-causing genePals1, which exhibit diminished cortices due to massive cell death, also exhibit nuclei enveloped by plasma membranes inside of dividing cells. These cell-in-cell (CIC) structures represent a dynamic process accompanied by lengthened mitosis and cytokinesis abnormalities. As shown in tumor cells, ROCK inhibition completely abrogates CIC structures and restores the normal length of mitosis. Moreover, genetic elimination ofTrp53produces a remarkable rescue of cortical size along with substantial reductions of CIC structures and cell death. These results provide a novel pathogenic mechanism by which microcephaly is produced through entotic cell cannibalism.
Germline TP53 mutations undergo copy number gain years prior to tumor diagnosis
Authors: Light Nicholas , Layeghifard Mehdi , Attery Ayush , Subasri Vallijah , Zatzman Matthew , Anderson Nathaniel D. , Hatkar Rupal , Blay Sasha , Chen David , Novokmet Ana , Fuligni Fabio , Tran James , de Borja Richard , Agarwal Himanshi , Waldman Larissa , Abegglen Lisa M. , Albertson Daniel , Finlay Jonathan L. , Hansford Jordan R. , Behjati Sam , Villani Anita , Gerstung Moritz , Alexandrov Ludmil B. , Somers Gino R. , Schiffman Joshua D. , Rotter Varda , Malkin David , Shlien Adam
Published: January 2023

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 pathogenic variants. Here, we perform whole-genome sequence (WGS) analysis of tumors from 22 patients with TP53 germline pathogenic variants. We observe somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous recombination genes as well as mutational signatures associated with prior chemotherapy. We identify near-ubiquitous early loss of heterozygosity of TP53, with gain of the mutant allele. This occurs earlier in these tumors compared to tumors with somatic TP53 mutations, suggesting the timing of this mark may distinguish germline from somatic TP53 mutations. Phylogenetic trees of tumor evolution, reconstructed from bulk and multi-region WGS, reveal that LFS tumors exhibit comparatively limited heterogeneity. Overall, our study delineates early copy number gains of mutant TP53 as a characteristic mutational process in LFS tumorigenesis, likely arising years prior to tumor diagnosis.
Pharmacotypes across the genomic landscape of pediatric acute lymphoblastic leukemia and impact on treatment response
Authors: Lee Shawn H. R. , Yang Wenjian , Gocho Yoshihiro , John August , Rowland Lauren , Smart Brandon , Williams Hannah , Maxwell Dylan , Hunt Jeremy , Yang Wentao , Crews Kristine R. , Roberts Kathryn G. , Jeha Sima , Cheng Cheng , Karol Seth E. , Relling Mary V. , Rosner Gary L. , Inaba Hiroto , Mullighan Charles G. , Pui Ching-Hon , Evans William E. , Yang Jun J.
Published: January 2023

Contemporary chemotherapy for childhood acute lymphoblastic leukemia (ALL) is risk-adapted based on clinical features, leukemia genomics and minimal residual disease (MRD); however, the pharmacological basis of these prognostic variables remains unclear. Analyzing samples from 805 children with newly diagnosed ALL from three consecutive clinical trials, we determined the ex vivo sensitivity of primary leukemia cells to 18 therapeutic agents across 23 molecular subtypes defined by leukemia genomics. There was wide variability in drug response, with favorable ALL subtypes exhibiting the greatest sensitivity to L-asparaginase and glucocorticoids. Leukemia sensitivity to these two agents was highly associated with MRD although with distinct patterns and only in B cell ALL. We identified six patient clusters based on ALL pharmacotypes, which were associated with event-free survival, even after adjusting for MRD. Pharmacotyping identified a T cell ALL subset with a poor prognosis that was sensitive to targeted agents, pointing to alternative therapeutic strategies. Our study comprehensively described the pharmacological heterogeneity of ALL, highlighting opportunities for further individualizing therapy for this most common childhood cancer.
Single-nucleus profiling of adult mice sub-ventricular zone after blast-related traumatic brain injury
Authors: Li Manrui , Chen Xiameng , Yang Qiuyun , Cao Shuqiang , Wyler Steven , Yuan Ruixuan , Zhang Lingxuan , Liao Miao , Lv Meili , Wang Feng , Guo Yadong , Zhou Jihong , Zhang Lin , Xie Xiaoqi , Liang Weibo
Published: January 2023

Explosive blast-related traumatic brain injuries (bTBI) are common in war zones and urban terrorist attacks. These bTBIs often result in complex neuropathologic damage and neurologic complications. However, there is still a lack of specific strategies for diagnosing and/or treating bTBIs. The sub-ventricular zone (SVZ), which undergoes adult neurogenesis, is critical for the neurological maintenance and repair after brain injury. However, the cellular responses and mechanisms that trigger and modulate these activities in the pathophysiological processes following bTBI remain poorly understood. Here we employ single-nucleus RNA-sequencing (snRNA-seq) of the SVZ from mice subjected to a bTBI. This data-set, including 15272 cells (7778 bTBI and 7494 control) representing all SVZ cell types and is ideally suited for exploring the mechanisms underlying the pathogenesis of bTBIs. Additionally, it can serve as a reference for future studies regarding the diagnosis and treatment of bTBIs.
Method to estimate the basal turn length in inner ear malformation types
Authors: Alshalan Afrah , Almuhawas Fida , Alhabib Salman , Hamed Nezar , Abdelsamad Yassin , Dhanasingh Anandhan
Published: January 2023

The mathematical equations to estimate cochlear duct length (CDL) using cochlear parameters such as basal turn diameter (A-value) and width (B-value) are currently applied for cochleae with two and a half turns of normal development. Most of the inner ear malformation (IEM) types have either  less than two and a half cochlear turns or have a cystic apex, making the current available CDL equations unsuitable for cochleae with abnormal anatomies. Therefore, this study aimed to estimate the basal turn length (BTL) from the cochlear parameters of different anatomical types, including normal anatomy; enlarged vestibular aqueduct; incomplete partition types I, II, and III; and cochlear hypoplasia. The lateral wall was manually tracked for 360° of the angular depth, along with the A and B values in the oblique coronal view for all anatomical types. A strong positive linear correlation was observed between BTL and the A- (r2 = 0.74) and B-values (r2 = 0.84). The multiple linear regression model to predict the BTL from the A-and B-values resulted in the following equation (estimated BTL = [A × 1.04] + [B × 1.89] − 0.92). The manually measured and estimated BTL differed by 1.12%. The proposed equation could be beneficial in adequately selecting an electrode that covers the basal turn in deformed cochleae.
New approaches for developing biomarkers of hormonal contraceptive use
Authors: Sachdeva Rakhee , Kumar Narender , Brache Vivian , Friedland Barbara A. , Plagianos Marlena , Zhang Shimin , Kizima Larisa , Cochon Leila , Tabar Ana Sofía Tejada , Blanc Ann , Merkatz Ruth B.
Published: January 2023

To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokinetics, we collected serum and urine samples before COC ingestion and during Days one and three of use, or before DMPA injection and on Days 21 and 60 post-injection. We used liquid chromatography-tandem mass spectrometry (LC–MS/MS) to measure serum/urine LNG and MPA. LNG was undetectable at baseline (specificity 100%); post ingestion, most urine samples had detectable LNG levels (sensitivity: 80% 6 h post Dose one, 93% 6 h post Dose three). We used a DetectX LNG immunoassay kit and showed 100% sensitivity measuring urine LNG. Urine MPA levels were undetectable in 14/15 women at baseline (specificity 91%); post-injection all urine samples had detectable MPA levels (sensitivity: 100% days 21 and 60). Results suggest urine sampling can be used to identify a biomarker of LNG and MPA use. Based on evidence from other steroidal hormonal studies showing changes affecting the transcriptome profile of saliva at 24 h, we used the same (COC, DMPA) timepoints to collect saliva. We performed transcriptome analysis and detected several differentially expressed genes in DMPA users’ saliva on Days 21 and 60 compared to baseline; none among COC users. We plan further research of differential gene expression in saliva as a HC biomarker of DMPA use, and will explore longer periods of COC use and saliva collection times, and application of microRNA sequencing to support using saliva as a COC biomarker.
Strength training for arterial hypertension treatment: a systematic review and meta-analysis of randomized clinical trials
Authors: Correia Rafael Ribeiro , Veras Allice Santos Cruz , Tebar William Rodrigues , Rufino Jéssica Costa , Batista Victor Rogério Garcia , Teixeira Giovana Rampazzo
Published: January 2023

Cardiovascular diseases are the leading cause of death in the world and arterial hypertension (AH) accounts for 13.8% of deaths caused by cardiovascular diseases. Strength training interventions could be an important alternative tool for blood pressure control, however, consistent evidence and the most effective training protocol for this purpose are yet to be established. The current study used the Cochrane methodology to systematically review randomized controlled trials (RCTs) that investigated the effect of strength training on blood pressure in hypertensive patients. A systematic search was conducted in the PubMed, EMBASE, Scopus, Cochrane Library, and World Health Organization databases. This review included controlled trials that evaluated the effect of strength training for 8 weeks or more in adults with arterial hypertension, published up to December 2020. Data are described and reported as the weighted mean difference of systolic and diastolic pressure and a 95% confidence interval. Protocol registration: PROSPERO registration number CRD42020151269. A total of 14 studies were identified, including a combined total of 253 participants with hypertension. The meta-analysis showed that mean values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly after strength training interventions. The strongest effect of strength training on decreasing blood pressure was observed in protocols with a moderate to vigorous load intensity (> 60% of one-repetition maximum-1RM), a frequency of at least 2 times per week, and a minimum duration of 8 weeks. We concluded that strength training interventions can be used as a non-drug treatment for arterial hypertension, as they promote significant decreases in blood pressure.
The greater wax moth, Galleria mellonella (L.) uses two different sensory modalities to evaluate the suitability of potential oviposition sites
Authors: Parepely Saravan Kumar , Kempraj Vivek , Sanganahalli Dharanesh Divija , Krishnarao Gandham , Pagadala Damodaram Kamala Jayanthi
Published: January 2023

An ovipositing insect evaluates the benefits and risks associated with the selection of an oviposition site for optimizing the fitness and survival of its offspring. The greater wax moth, Galleria mellonella (L.), uses beehives as an oviposition site. During egg-laying, the gravid wax moth confronts two kinds of risks, namely, bees and conspecific larvae. While bees are known to attack the moth’s offspring and remove them from the hive, the conspecific larvae compete for resources with the new offspring. To date, little is known about the mechanisms involved in the assessment of oviposition site by the greater wax moth, G. mellonella (L.). Here, we demonstrate that the wax moth uses two different sensory modalities to detect risks to its offspring in the hives of Apis cerena. Bees appear to be detected by the contact-chemoreception system of the gravid wax moth, while detection of conspecifics relies on the olfactory system. Hence, our findings suggest that two different sensory modalities are used to detect two different risks to the offspring and that the selection of oviposition sites by G. mellonella (L.) relies on the integration of inputs from both the olfactory and contact-chemoreception systems.
Cold- versus warm-season-forced variability of the Kuroshio and North Pacific subtropical mode water
Authors: Kawakami Yuma , Nakano Hideyuki , Urakawa L. Shogo , Toyoda Takahiro , Sakamoto Kei , Yamanaka Goro , Sugimoto Shusaku
Published: January 2023

The ocean responds to atmospheric variations. Changes in sea surface winds, surface air temperature, and surface air humidity cause upper ocean variability by modulating air-sea momentum and heat exchanges. Upper ocean variability in the mid-latitudes on inter-annual and longer timescales has previously been considered to be attributable to atmospheric variations in the cold season, because atmospheric forcing is stronger in the cold season than in the warm season. However, this idea has not been sufficiently confirmed yet. Although the ocean model is a useful tool to evaluate the impact of the atmospheric forcing in each season, there are no past studies having examined ocean model responses respectively to the cold- and warm-season atmospheric forcing. In this study, we performed numerical experiments with an eddy-resolving ocean general circulation model and investigated oceanic responses to cold- and warm-season atmospheric forcing, focusing on the Kuroshio and North Pacific subtropical mode water (STMW) in the western mid-latitude North Pacific. We found that temporal variations of net Kuroshio transport and STMW distribution/temperature are dominantly controlled by atmospheric forcing in the cold season. These results suggest that cold-season atmospheric variations are key to obtaining insights into large-scale upper ocean variability in the North Pacific subtropical gyre.
Solar radiation, temperature and the reproductive biology of the coral Lobactis scutaria in a changing climate
Authors: Bouwmeester Jessica , Daly Jonathan , Zuchowicz Nikolas , Lager Claire , Henley E. Michael , Quinn Mariko , Hagedorn Mary
Published: January 2023

Coral reefs worldwide are at risk due to climate change. Coral bleaching is becoming increasingly common and corals that survive bleaching events can suffer from temporary reproductive failure for several years. While water temperature is a key driver in causing coral bleaching, other environmental factors are involved, such as solar radiation. We investigated the individual and combined effects of temperature, photosynthetically active radiation (PAR), and ultraviolet radiation (UVR) on the spawning patterns and reproductive physiology of the Hawaiian mushroom coral Lobactis scutaria, using long-term experiments in aquaria. We examined effects on spawning timing, fertilisation success, and gamete physiology. Both warmer temperatures and filtering UVR altered the timing of spawning. Warmer temperatures caused a drop in fertilisation success. Warmer temperatures and higher PAR both negatively affected sperm and egg physiology. These results are concerning for the mushroom coral L. scutaria and similar reproductive data are urgently needed to predict future reproductive trends in other species. Nonetheless, thermal stress from global climate change will need to be adequately addressed to ensure the survival of reef-building corals in their natural environment throughout the next century and beyond. Until then, reproduction is likely to be increasingly impaired in a growing number of coral species.
Bio-inspired antimicrobial surfaces fabricated by glancing angle deposition
Authors: Qu Chuang , Rozsa Jesse L. , Jung Hyun-Jin , Williams Anna R. , Markin Emmanuel K. , Running Mark P. , McNamara Shamus , Walsh Kevin M.
Published: January 2023

This paper describes the fabrication of cicada-wing-inspired antimicrobial surfaces using Glancing Angle Deposition (GLAD). From the study of an annual cicada (Neotibicen Canicularis, also known as dog-day cicada) in North America, it is found that the cicada wing surfaces are composed of unique three-dimensional (3D) nanofeature arrays, which grant them extraordinary properties including antimicrobial (antifouling) and antireflective. However, the morphology of these 3D nanostructures imposes challenges in artificially synthesizing the structures by utilizing and scaling up the template area from nature. From the perspective of circumventing the difficulties of creating 3D nanofeature arrays with top-down nanofabrication techniques, this paper introduces a nanofabrication process that combines bottom-up steps: self-assembled nanospheres are used as the bases of the features, while sub-100 nm pillars are grown on top of the bases by GLAD. Scanning electron micrographs show the resemblance of the synthesized cicada wing mimicry samples to the actual cicada wings, both quantitatively and qualitatively. The synthetic mimicry samples are hydrophobic with a water contact angle of 125˚. Finally, the antimicrobial properties of the mimicries are validated by showing flat growth curves of Escherichia coli (E. coli) and by direct observation under scanning electron microscopy (SEM). The process is potentially suitable for large-area antimicrobial applications in food and biomedical industries.
Long-term presence of autoantibodies in plasma of cured leprosy patients
Authors: Yang Xi , Dong Hua , Kuang Yi-Qun , Yu Xiu-Feng , Long Heng , Zhang Chun-Yu , Wang Dong , Zhang Deng-Feng , Li Yu-Ye
Published: January 2023

Autoantibodies have been detected in leprosy patients, indicating that infection with M. leprae may lead to autoimmune disorders. However, whether autoimmune response last until patients are cured is unknown. Knowing the autoimmune response in cured leprosy patients is essential to identify whether symptoms are caused by leprosy itself or by other immune-related diseases. This knowledge is essential for the ongoing health management in cured leprosy patients where autoimmune disorders still exist. In our study, we selected six autoantibodies, including anticardiolipin antibody of IgG (ACA), anti-nuclear antibody (ANA), extractable nuclear antigen antibody (ENA), anti-streptolysin O (ASO), anti-double stranded DNA antibody (dsDNA), and rheumatoid factor (RF), that had been reported in leprosy patients as typical autoantibodies. We tested the six typical autoantibodies combined with LACC1, which encodes a protein associated with autoimmune disease such as Crohn’s disease and is also the susceptible gene conferring leprosy risk, in cured leprosy patients through ELISA to assess the cured patient’s immune status. We observed high positive rates of autoantibodies in cured leprosy patients, and the average plasma levels of five (ACA, ANA, ENA, ASO, and RF) out of the six autoantibodies were significantly higher in cured leprosy patients than in controls. The positive detection of autoantibodies is independent of the recovery period. Moreover, the level of these autoantibodies showed a strong positive correlation with the level of LACC1 in both controls and cured patients. This study showed that there is long-term autoimmunological activation in leprosy patients, even after decades of recovery. Autoimmune responses may influence the development and prognosis of leprosy. Special care should be given to posttreatment or cured leprosy patients regarding long-term autoimmunological activation.