bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strong Climate Control on the Millennial‐Scale Dust Variability and Sediment Provenances in the Equatorial Indian Ocean Inferred From Sr‐Nd Isotopes
Authors: Shukla Arvind , Singh Sunil Kumar , Singh Dharmendra Pratap , Sharma Aka , Dimri A. P. 
Published: March 2024

AbstractHigh‐resolution Sr and Nd isotope compositions along with major and trace element abundances have been analyzed in silicate fraction of sediments core, SSD004‐GC03, from the Equatorial Indian Ocean (7.2°N and 77.9°E) at 1,540 m water depth with a depositional history of ∼38 ka to determine source variabilities and their controlling factors. 87Sr/86Sr (0.71978–0.72491), ƐNd (−14.8 to −21.9), and a couple of source diagnostic elements display profound variability over the depositional time scale and point toward major sediment contribution from the Peninsular Gneissic Complex (PGC) and the Deccan Basalts along with aeolian dust flux, their relative proportions being determined by climate variability. The cold/arid periods are characterized by an enhanced proportion of aeolian dust and the Deccan Basalts, whereas the sediment contribution from the PGC is augmented during the warm/humid periods. The sediment provenance variations at the Equatorial Indian Ocean coincide very well with known cold/arid (Heinrich Stadial events: HS 1–4, LGM, Younger Dryas, 8.2 ka, 5.2 ka, and 1.1 ka) and warm/humid (Early Deglacial, Holocene Intensified Monsoon) climatic events reported in the tropical region and sea‐level change which are strongly captured by the Sr‐Nd isotope and elemental composition of sediments. The present investigation underscores the significant role of climate, mainly the aridity, in modulating the dust fluxes and erosion intensity and the strong coupling between Indian monsoon and North Atlantic climatic oscillations and further demonstrates minimal time delay between the production and transport of sediment from source to sink.
New insights into the clinical and molecular spectrum of the MADD-related neurodevelopmental disorder
Authors: Abdel-Salam Ghada M. H. , Abdel-Hamid Mohamed S. 
Published: March 2024

AbstractBiallelic pathogenic variants in MADD lead to a very rare neurodevelopmental disorder which is phenotypically pleiotropic grossly ranging from severe neonatal hypotonia, failure to thrive, multiple organ dysfunction, and early lethality to a similar but milder phenotype with better survival. Here, we report 5 patients from 3 unrelated Egyptian families in whom 4 patients showed the severe end of the spectrum displaying neonatal respiratory distress, hypotonia and chronic diarrhea while one patient presented with the mild form displaying moderate intellectual disability and myopathy. In addition, we observed distal arthrogryposis and nonspecific structural brain anomalies in all our patients. Interestingly, cerebellar and brainstem hypoplasia were noted in one patient. Whole exome sequencing identified three novel homozygous variants in the MADD gene: two likely pathogenic [c.4321delC p.(Gln1441ArgfsTer46) and c.2620 C > T p.(Arg874Ter)] and one variant of uncertain significance (c.4307 G > A, p.Arg1436Gln). The variants segregated with the disease in all available family members. Our findings confirm that arthrogryposis, genital, cardiac and structural brain anomalies are manifestations of MADD which expand the spectrum of MADD-related neurodevelopmental disorder. Moreover, they further highlight the convergence of MADD variants on different organ systems leading to complex phenotypes.
A bird’s eye view on the use of whole exome sequencing in rare congenital ophthalmic diseases
Authors: Zucco Jessica , Baldan Federica , Allegri Lorenzo , Bregant Elisa , Passon Nadia , Franzoni Alessandra , D’Elia Angela Valentina , Faletra Flavio , Damante Giuseppe , Mio Catia 
Published: March 2024

AbstractPhenotypic and genotypic heterogeneity in congenital ocular diseases, especially in anterior segment dysgenesis (ASD), have created challenges for proper diagnosis and classification of diseases. Over the last decade, genomic research has indeed boosted our understanding in the molecular basis of ASD and genes associated with both autosomal dominant and recessive patterns of inheritance have been described with a wide range of expressivity. Here we describe the molecular characterization of a cohort of 162 patients displaying isolated or syndromic congenital ocular dysgenesis. Samples were analyzed with diverse techniques, such as direct sequencing, multiplex ligation-dependent probe amplification, and whole exome sequencing (WES), over 20 years. Our data reiterate the notion that PAX6 alterations are primarily associated with ASD, mostly aniridia, since the majority of the cohort (66.7%) has a pathogenic or likely pathogenic variant in the PAX6 locus. Unexpectedly, a high fraction of positive samples (20.3%) displayed deletions involving the 11p13 locus, either partially/totally involving PAX6 coding region or abolishing its critical regulatory region, underlying its significance. Most importantly, the use of WES has allowed us to both assess variants in known ASD genes (i.e., CYP1B1, ITPR1, MAB21L1, PXDN, and PITX2) and to identify rarer phenotypes (i.e., MIDAS, oculogastrointestinal-neurodevelopmental syndrome and Jacobsen syndrome). Our data clearly suggest that WES allows expanding the analytical portfolio of ocular dysgenesis, both isolated and syndromic, and that is pivotal for the differential diagnosis of those conditions in which there may be phenotypic overlaps and in general in ASD.
Structured lifestyle modification as an adjunct to obesity pharmacotherapy: there is much to learn
Authors: Murphy Enda , Finucane Francis Martin 
Published: March 2024

AbstractWe are at the start of an exciting new era of very effective pharmacotherapy for patients with obesity, with the latest generation of drugs approaching the efficacy of obesity surgery. Clinical trials of obesity drugs tend to emphasise the importance of participation in some form of structured lifestyle intervention for all trial participants. This usually consists of advice to reduce calorie intake and increase moderate to vigorous physical activity. There is strong evidence that structured lifestyle modification programmes improve health in patients with obesity and related disorders. However, there is no specific evidence that they improve the response to obesity medications. This is because of the way that drug trials for patients with obesity have traditionally been designed, with participants in the active drug treatment group being compared to participants on placebo drug treatment, but with both groups always receiving the same structured lifestyle intervention. While this approach is entirely reasonable, it makes it impossible to draw any inferences about the efficacy of structured lifestyle modification to augment the response to drug therapy. Given this genuine equipoise, a critical step in ensuring that our treatment of patients with obesity is robustly evidence-based is to determine whether “drug plus lifestyle” offer any advantage over “drug plus placebo” in large, well-designed and adequately powered clinical trials. We also need to determine the cost-effectiveness of these programmes.
Hematopoietic cell transplantation and cell therapy activity landscape survey in the Kingdom of Saudi Arabia; a report from the Saudi Society of Blood and Marrow Transplantation (SSBMT)
Authors:   On behalf of Saudi Society of Blood & Marrow Transplantation (SSBMT), Shaheen Naila , Abosoudah Ibrahim , Alshahrani Mohammad , Alzahrani Mohsen , Essa Mohammed , Alahmari Bader , Mutaher Enas , Kanfar Solaf , Alsaeed Ahmad , Alamoudi Sameer , Monagel Dania , Marei Mohammed , Alzahrani Musa , Alsultan Abdulrahman , Aljefri Abdullah , Masari Ahlam , Alsharif Omer , Alsughayir Ammar H. , Hejazi Ayman , Aldaama Saad , Alaskar Ahmed 
Published: March 2024

AbstractHematopoietic Cell Transplantation (HCT) activity was surveyed in the Kingdom of Saudi Arabia (KSA). The overall rate of HCT per 10,000,000 inhabitants doubled every 10 years. 15,031 HCTs were reported by all the functional HCT centers in KSA since inception of HCT program. Out of total HCT 15,031; 10,232(68%) were reported in adults, and 4799(32%) in the pediatric population. Allogeneic HCT constituted 10,489(70%) of total HCT, with majority from Human Leukocyte Antigen matched identical sibling (85.4%). The autologous HCTs were 4542(30%). During the last five years 2018–2022; in total 5164 HCTs were performed, with the majority had allogeneic HCT 3,085(59.74%), followed by the autologous HCT 3085(40.2%). The top three main indications of the autologous HCT were Multiple Myeloma 299(28%), Hodgkin Lymphoma 293(27.8%), and Non-Hodgkin Lymphoma 212(20%). Hemoglobinopathies 615(27.6%) were mostly indicated for allogeneic HCT, followed by Acute Myeloid Leukemia 433(19.4%), and Precursors Lymphoid Neoplasms 322(14.4%). The HCT activity landscape survey provides the updated current state and trends for HCT in KSA. The reported HCT numbers differ than what was reported by international registries, since not all the cases have been reported. We urge to have a common data hub nationally in order to capture the actual number of cases.
Investigating the cut-off values of captopril challenge test for primary aldosteronism using the novel chemiluminescent enzyme immunoassay method: a retrospective cohort study
Authors: Tezuka Yuta , Omata Kei , Ono Yoshikiyo , Kambara Kengo , Kamada Hiroki , Oguro Sota , Yamazaki Yuto , Gomez-Sanchez Celso E. , Ito Akihiro , Sasano Hironobu , Takase Kei , Tanaka Tetsuhiro , Katagiri Hideki , Satoh Fumitoshi 
Published: March 2024

AbstractThe measurement evolution enabled more accurate evaluation of aldosterone production in hypertensive patients. However, the cut-off values for novel assays have been not sufficiently validated. The present study was undertaken to validate the novel chemiluminescent enzyme immunoassay for aldosterone in conjunction with other methods. Moreover, we also aimed to establish a new cut-off value for primary aldosteronism in the captopril challenge test using the novel assay. First, we collected 390 plasma samples, in which aldosterone levels measured using liquid chromatography-mass spectrometry ranged between 0.18 and 1346 ng/dL. The novel chemiluminescent enzyme immunoassay showed identical correlation of plasma aldosterone with liquid chromatography-mass spectrometry, in contrast to conventional radioimmunoassay. Further, we enrolled 299 and 39 patients with primary aldosteronism and essential hypertension, respectively. Plasma aldosterone concentrations measured using the novel assay were lower than those measured by radioimmunoassay, which resulted in decreased aldosterone-to-renin ratios. Subsequently, positive results of the captopril challenge test based on radioimmunoassay turned into “negative” based on the novel assay in 45% patients with primary aldosteronism, using the conventional cut-off value (aldosterone-to-renin activity ratio > 20 ng/dL per ng/mL/h). Receiver operating characteristic curve analysis demonstrated that aldosterone-to-renin activity ratios > 8.2 ng/dL per ng/mL/h in the novel assay was compatible with the conventional diagnosis (sensitivity, 0.874; specificity, 0.980). Our study indicates the great measurement accuracy of the novel chemiluminescent enzyme immunoassay for aldosterone, and the importance of measurement-adjusted cut-offs in the diagnosis of primary aldosteronism.
Modulation of DBS-induced cortical responses and movement by the directionality and magnitude of current administered
Authors: Spooner Rachel K. , Hizli Baccara J. , Bahners Bahne H. , Schnitzler Alfons , Florin Esther 
Published: March 2024

AbstractSubthalamic deep brain stimulation (STN-DBS) is an effective therapy for alleviating motor symptoms in people with Parkinson’s disease (PwP), although some may not receive optimal clinical benefits. One potential mechanism of STN-DBS involves antidromic activation of the hyperdirect pathway (HDP), thus suppressing cortical beta synchrony to improve motor function, albeit the precise mechanisms underlying optimal DBS parameters are not well understood. To address this, 18 PwP with STN-DBS completed a 2 Hz monopolar stimulation of the left STN during MEG. MEG data were imaged in the time-frequency domain using minimum norm estimation. Peak vertex time series data were extracted to interrogate the directional specificity and magnitude of DBS current on evoked and induced cortical responses and accelerometer metrics of finger tapping using linear mixed-effects models and mediation analyses. We observed increases in evoked responses (HDP ~ 3–10 ms) and synchronization of beta oscillatory power (14–30 Hz, 10–100 ms) following DBS pulse onset in the primary sensorimotor cortex (SM1), supplementary motor area (SMA) and middle frontal gyrus (MFG) ipsilateral to the site of stimulation. DBS parameters significantly modulated neural and behavioral outcomes, with clinically effective contacts eliciting significant increases in medium-latency evoked responses, reductions in induced SM1 beta power, and better movement profiles compared to suboptimal contacts, often regardless of the magnitude of current applied. Finally, HDP-related improvements in motor function were mediated by the degree of SM1 beta suppression in a setting-dependent manner. Together, these data suggest that DBS-evoked brain-behavior dynamics are influenced by the level of beta power in key hubs of the basal ganglia-cortical loop, and this effect is exacerbated by the clinical efficacy of DBS parameters. Such data provides novel mechanistic and clinical insight, which may prove useful for characterizing DBS programming strategies to optimize motor symptom improvement in the future.
Implementation of pooled saliva tests for universal screening of cCMV infection
Authors: Merav Lior , Ofek Shlomai Noa , Oiknine-Djian Esther , Caplan Orit , Livneh Ayala , Sido Tal , Peri Amir , Shtoyer Aviad , Amir Eden , Ben Meir Kerem , Daitch Yutti , Rivkin Mila , Kripper Esther , Fogel Irit , Horowitz Hadar , Greenberger Sraya , Cohen Mevaseret , Geal-Dor Miriam , Gordon Oren , Averbuch Diana , Ergaz-Shaltiel Zivanit , Eventov Friedman Smadar , Wolf Dana G. , Yassour Moran 
Published: March 2024

AbstractCongenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to neurodevelopmental disabilities. Universal newborn infant screening of cCMV has been increasingly advocated. In the absence of a high-throughput screening test, which can identify all infected newborn infants, the development of an accurate and efficient testing strategy has remained an ongoing challenge. Here we assessed the implementation of pooled saliva polymerase chain reaction (PCR) tests for universal screening of cCMV, in two hospitals of Jerusalem from April 2022 through April 2023. During the 13-month study period, 15,805 infants (93.6% of all live newborn infants) were screened for cCMV using the pooled approach that has since become our routine screening method. The empirical efficiency of the pooling was six (number of tested newborn infants per test), thereby sparing 83% of the saliva tests. Only a minor 3.05 PCR cycle loss of sensitivity was observed for the pooled testing, in accordance with the theoretical prediction for an eight-sample pool. cCMV was identified in 54 newborn infants, with a birth prevalence of 3.4 per 1,000; 55.6% of infants identified with cCMV were asymptomatic at birth and would not have been otherwise targeted for screening. The study demonstrates the wide feasibility and benefits of pooled saliva testing as an efficient, cost-sparing and sensitive approach for universal screening of cCMV.
Structure and interactions of the endogenous human Commander complex
Authors: Laulumaa Saara , Kumpula Esa-Pekka , Huiskonen Juha T. , Varjosalo Markku 
Published: March 2024

AbstractThe Commander complex, a 16-protein assembly, plays multiple roles in cell homeostasis, cell cycle and immune response. It consists of copper-metabolism Murr1 domain proteins (COMMD1–10), coiled-coil domain-containing proteins (CCDC22 and CCDC93), DENND10 and the Retriever subcomplex (VPS26C, VPS29 and VPS35L), all expressed ubiquitously in the body and linked to various diseases. Here, we report the structure and key interactions of the endogenous human Commander complex by cryogenic-electron microscopy and mass spectrometry-based proteomics. The complex consists of a stable core of COMMD1–10 and an effector containing DENND10 and Retriever, scaffolded together by CCDC22 and CCDC93. We establish the composition of Commander and reveal major interaction interfaces. These findings clarify its roles in intracellular transport, and uncover a strong association with cilium assembly, and centrosome and centriole functions.
Structure of the human outer kinetochore KMN network complex
Authors: Yatskevich Stanislau , Yang Jing , Bellini Dom , Zhang Ziguo , Barford David 
Published: March 2024

AbstractFaithful chromosome segregation requires robust, load-bearing attachments of chromosomes to the mitotic spindle, a function accomplished by large macromolecular complexes termed kinetochores. In most eukaryotes, the constitutive centromere-associated network (CCAN) complex of the inner kinetochore recruits to centromeres the ten-subunit outer kinetochore KMN network that comprises the KNL1C, MIS12C and NDC80C complexes. The KMN network directly attaches CCAN to microtubules through MIS12C and NDC80C. Here, we determined a high-resolution cryo-EM structure of the human KMN network. This showed an intricate and extensive assembly of KMN subunits, with the central MIS12C forming rigid interfaces with NDC80C and KNL1C, augmented by multiple peptidic inter-subunit connections. We also observed that unphosphorylated MIS12C exists in an auto-inhibited state that suppresses its capacity to interact with CCAN. Ser100 and Ser109 of the N-terminal segment of the MIS12C subunit Dsn1, two key targets of Aurora B kinase, directly stabilize this auto-inhibition. Our study indicates how selectively relieving this auto-inhibition through Ser100 and Ser109 phosphorylation might restrict outer kinetochore assembly to functional centromeres during cell division.
A chromosome-level genome assembly of yellow stem borer (Scirpophaga incertulas)
Authors: Zhou Sicong , Luo Guanghua , Yang Qiong , Han Yangchun , Yuan Kaili , Ji Rui , Fang Jichao 
Published: March 2024

AbstractThe yellow stem borer Scirpophaga incertulas is the dominant pest of rice in tropical Asia. However, the lack of genomic resources makes it difficult to understand their invasiveness and ecological adaptation. A high-quality chromosome-level genome of S. incertulas, a monophagous rice pest, was assembled by combining Illumina short reads, PacBio HiFi long sequencing, and Hi-C scaffolding technology. The final genome size was 695.65 Mb, with a scaffold N50 of 28.02 Mb, and 93.50% of the assembled sequences were anchored to 22 chromosomes. BUSCO analysis demonstrated that this genome assembly had a high level of completeness, with 97.65% gene coverage. A total of 14,850 protein-coding genes and 366.98 Mb of transposable elements were identified. In addition, comparative genomic analyses indicated that chemosensory processes and detoxification capacity may play critical roles in the specialized host preference of S. incertulas. In summary, the chromosome-level genome assembly of S. incertulas provides a valuable genetic resource for understanding the biological characteristics of its invasiveness and developing an efficient management strategy.
Evaluating the lifetime performance index of omega distribution based on progressive type-II censored samples
Authors: Kilany N. M. , El-Refai Lobna H. 
Published: March 2024

AbstractBesides achieving high quality products, statistical techniques are applied in many fields associated with health such as medicine, biology and etc. Adhering to the quality performance of an item to the desired level is a very important issue in various fields. Process capability indices play a vital role in evaluating the performance of an item. In this paper, the larger-the-better process capability index for the three-parameter Omega model based on progressive type-II censoring sample is calculated. On the basis of progressive type-II censoring the statistical inference about process capability index is carried out through the maximum likelihood. Also, the confidence interval is proposed and the hypothesis test for estimating the lifetime performance of products. Gibbs within Metropolis–Hasting samplers procedure is used for performing Markov Chain Monte Carlo (MCMC) technique to achieve Bayes estimation for unknown parameters. Simulation study is calculated to show that Omega distribution's performance is more effective. At the end of this paper, there are two real-life applications, one of them is about high-performance liquid chromatography (HPLC) data of blood samples from organ transplant recipients. The other application is about real-life data of ball bearing data. These applications are used to illustrate the importance of Omega distribution in lifetime data analysis.
Effectiveness of COVID-19 vaccines among children 6–11 years against hospitalization during Omicron predominance in Malaysia
Authors: Jayaraj Vivek Jason , Husin Masliyana , Suah Jing Lian , Tok Peter Seah Keng , Omar Azahadi , Rampal Sanjay , Sivasampu Sheamini 
Published: March 2024

AbstractThere is currently limited data on the effectiveness of COVID-19 vaccines for children aged 6–11 years in Malaysia. This study aims to determine vaccine effectiveness (VE) against COVID-19-related hospitalization after receipt of one- and two-doses of BNT162b2 mRNA (Comirnaty-Pfizer/BioNTech) vaccine over a duration of almost 1 year in the predominantly Omicron period of BA.4/BA.5 and X.B.B sub lineages. This study linked administrative databases between May 2022 and March 2023 to evaluate real-world vaccine effectiveness (VE) for the BNT162b2 mRNA (Comirnaty-Pfizer/BioNTech) vaccine against COVID-19-related hospitalization in the Omicron pre-dominant period with BA.4/BA.5 and X.B.B sub lineages. During the Omicron-predominant period, the cumulative hospitalization rate was almost two times higher for unvaccinated children (9.6 per million population) compared to vaccinated children (6 per million population). The estimated VE against COVID-19 hospitalization for one dose of BNT162b2 was 27% (95% CI − 1%, 47%) and 38% (95% CI 27%, 48%) for two doses. The estimated VE against hospitalization remained stable when stratified by time. VE for the first 90 days was estimated to be 45% (95% CI 33, 55%), followed by 47% (95% CI 34, 56%) between 90 and 180 days, and 36% (95% CI 22, 45%) between 180 and 360 days. Recent infection within 6 months does not appear to modify the impact of vaccination on the risk of hospitalization, subject to the caveat of potential underestimation. In our pediatric population, BNT162b2 provided moderate-non-diminishing protection against COVID-19 hospitalization over almost 1 year of Omicron predominance.