bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of data for planning and service improvement in Tanzanian Primary healthcare facilities: Experience from Star Rating Assessment
Authors: German Chrisogone C. , Yahya Talhiya A. , Hokororo Joseph C. , Kinyenje Erick S. , Nungu Saumu I. , Mohamed Mohamed A. , Degeh Mbwana M. , Nassoro Omary A. , Mwaisengela Syabo M. , Bahegwa Radenta P. , Msigwa Yohanes S. , Ngowi Ruth R. , Marandu Laura E. , Eliakimu Eliudi S. 
Published: June 2022

ABSTRACTBackgroundThe use of data for planning and improving healthcare delivery is sub-optimal among developing countries. In 2015, Tanzania started to implement Star Rating Assessment (SRA) process for primary health care (PHC) facilities to improve various dimensions of quality of services, including the use of data. We aimed at assessing the extent and predictors of data use in Tanzanian PHC facilities.MethodologyWe used the most current national SRA data available in DHIS2 that was collected in 2017/2018 from all 7,289 PHC facilities. A facility was considered using data if gained 80% of the allocated scores. Other dependent variables were the three components that together contribute to the use of data [If PHC facility has Health Management Information systems (HMIS) functional, disseminate information, and has proper medical records]. We determined the association between data use and facility ownership status (public or private), location of the facility (rural or urban) and facility service level (dispensary, health centre or hospital). Results are presented as proportions of facilities that qualified for data use and the three components. The associations are reported in Adjusted odds ratio (AOR) with a 95% confidence interval (CI).ResultsA total of 6,663(91.4%) PHC facilities met our inclusion criteria for analysis. Among the facilities: 1,198(18.0%) had used data for planning and services improvement; 3,792(56.9%) had functional HMIS; 1,752(26.3%) had disseminated data; and 631(9.5%) had proper medical records. PHC facilities that are publicly owned (AOR 1.25; 95% CI: 1.05–1.48) and those at higher service level [hospitals (AOR 1.77; 95% CI: 1.27–2.46) and health centres (AOR 1.39; 95% CI: 1.15–1.68) compared to dispensaries] were more likely to use data.ConclusionThe use of facility data for planning and services improvement in Tanzanian PHC facilities is low, and much effort needs to be targeted at privately-owned and low-level PHC facilities.
Waning of two-dose BNT162b2 and mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection is robust to depletion-of-susceptibles bias
Authors: Andrejko Kristin L. , Pry Jake , Myers Jennifer F. , Mehrotra Megha , Lamba Katherine , Lim Esther , Fukui Nozomi , DeGuzman Jennifer L. , Openshaw John , Watt James , Jain Seema , Lewnard Joseph A. 
Published: June 2022

ABSTRACTConcerns about the duration of protection conferred by COVID-19 vaccines have arisen in postlicensure evaluations. However, “depletion of susceptibles” bias driven by differential accrual of infection among vaccinated and unvaccinated individuals may contribute to the appearance of waning vaccine effectiveness (VE) in epidemiologic studies, potentially hindering interpretation of estimates. We enrolled California residents who received molecular SARS-CoV-2 tests in a matched, test-negative design case-control study to estimate VE of mRNA-based COVID-19 vaccines between 23 February and 5 December 2021. We analyzed waning protection following 2 vaccine doses using conditional logistic regression models. Additionally, we used data from case-based surveillance along with estimated case-to-infection ratios from a population-based serological study to quantify the potential contribution of the “depletion-of-susceptibles” bias to time-varying VE estimates for 2 doses. We also estimated VE for 3 doses relative to 0 doses and 2 doses, by time since second dose receipt. Pooled VE of BNT162b2 and mRNA-1273 against symptomatic SARS-CoV-2 infection was 91.3% (95% confidence interval: 83.8-95.4%) at 14 days after second-dose receipt and declined to 50.8% (31.2-75.6%) at 7 months. Accounting for differential depletion-of-susceptibles among vaccinated and unvaccinated individuals, we estimated VE was 53.2% (23.6-71.2%) at 7 months among individuals who had completed the primary series (2 doses). With receipt of a third dose of BN162b2 or mRNA-1273, VE increased to 95.0% (82.8-98.6%), compared with zero doses. These findings confirm that observed waning of protection is not attributable to epidemiologic bias and support ongoing efforts to administer additional vaccine doses to mitigate burden of COVID-19.
Genetic Diversity and Evolutionary Convergence of Cryptic SARS-CoV-2 Lineages Detected Via Wastewater Sequencing
Authors: Gregory Devon A. , Trujillo Monica , Rushford Clayton , Flury Anna , Kannoly Sherin , San Kaung Myat , Lyfoung Dustin , Wiseman Roger W. , Bromert Karen , Zhou Ming-Yi , Kesler Ellen , Bivens Nathan , Hoskins Jay , Lin Chung-Ho , O’Connor David H. , Wieberg Chris , Wenzel Jeff , Kantor Rose S. , Dennehy John J. , Johnson Marc C. 
Published: June 2022

AbstractWastewater-based epidemiology (WBE) is an effective way of tracking the appearance and spread of SARS-COV-2 lineages through communities. Beginning in early 2021, we implemented a targeted approach to amplify and sequence the receptor binding domain (RBD) of SARS-COV-2 to characterize viral lineages present in sewersheds. Over the course of 2021, we reproducibly detected multiple SARS-COV-2 RBD lineages that have never been observed in patient samples in 9 sewersheds located in 3 states in the USA. These cryptic lineages contained between 4 to 24 amino acid substitutions in the RBD and were observed intermittently in the sewersheds in which they were found for as long as 14 months. Many of the amino acid substitutions in these lineages occurred at residues also mutated in the Omicron variant of concern (VOC), often with the same substitution. One of the sewersheds contained a lineage that appeared to be derived from the Alpha VOC, but the majority of the lineages appeared to be derived from pre-VOC SARS-COV-2 lineages. Specifically, several of the cryptic lineages from New York City appeared to be derived from a common ancestor that most likely diverged in early 2020. While the source of these cryptic lineages has not been resolved, it seems increasingly likely that they were derived from immunocompromised patients or animal reservoirs. Our findings demonstrate that SARS-COV-2 genetic diversity is greater than what is commonly observed through routine SARS-CoV-2 surveillance. Wastewater sampling may more fully capture SARS-CoV-2 genetic diversity than patient sampling and could reveal new VOCs before they emerge in the wider human population.Author SummaryDuring the COVID-19 pandemic, wastewater-based epidemiology has become an effective public health tool. Because many infected individuals shed SARS-CoV-2 in feces, wastewater has been monitored to reveal infection trends in the sewersheds from which the samples were derived. Here we report novel SARS-CoV-2 lineages in wastewater samples obtained from 3 different states in the USA. These lineages appeared in specific sewersheds intermittently over periods of up to 14 months, but generally have not been detected beyond the sewersheds in which they were initially found. Many of these lineages may have diverged in early 2020. Although these lineages share considerable overlap with each other, they have never been observed in patients anywhere in the world. While the wastewater lineages have similarities with lineages observed in long-term infections of immunocompromised patients, animal reservoirs cannot be ruled out as a potential source.
Investigating Causal Relationships between Inflammatory Bowel Disease and Autism Spectrum Disorder: A Bidirectional Two-sample Mendelian Randomization Study
Authors: Zeng Ruijie , Jiang Rui , Wang Jinghua , Yang Jie , Wu Huihuan , Zhuo Zewei , Yang Qi , Li Jingwei , Liao Songyan , Tse Hung-Fat , Sha Weihong , Chen Hao 
Published: June 2022

AbstractBackground and aimsInflammatory bowel disease (IBD) is usually comorbid with psychological disorders. Emerging observational studies have indicated the association between autism spectrum disorder (ASD) and IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), whereas the causality remains unknown. Our study aimed to explore the causal association between IBD and ASD using bidirectional two-sample Mendelian randomization (MR) design.MethodsSummary-level data from large-scale genome-wide association (GWAS) studies of IBD (International Inflammatory Bowel Disease Genetics Consortium, Ncases=25,042, Ncontrols=34,915) and ASD (Integrative Psychiatric Research-Psychiatric Genomics Consortium, Ncases=18,382, Ncontrols=27,969) were retrieved. Gene variants for IBD and ASD were selected as instrumental variables. MR analyses were performed mainly including the inverse-variance-weighted method with a series of sensitivity tests.ResultsGenetic predisposition to IBD was associated with a high risk of ASD (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01-1.06, P = 0.01; OR [95% CI]: 1.03 [1.01-1.05], P = 0.02 for CD; OR [95% CI]: 1.03 [1.01-1.07], P = 0.04 for UC). In contrast, no causal association was found for the genetic liability to ASD on IBD.ConclusionsOur findings reveal that genetically predicted IBD is causally related to ASD, whereas the causal association of ASD on IBD is not supported. Our study highlights the early screening and surveillance of psychological symptoms, as well as sustaining support for patients with IBD. Further investigations on age-specific groups are warranted.
Bayesian multi-level calibration of a process-based maize phenology model
Authors: Viswanathan Michelle , Scheidegger Andreas , Streck Thilo , Gayler Sebastian , Weber Tobias KD 
Published: June 2022

AbstractPlant phenology models are important components in process-based crop models, which are used to assess the impact of climate change on food production. For reliable model predictions, parameters in phenology models have to be accurately known. They are usually estimated by calibrating the model to observations. However, at regional scales in which different cultivars of a crop species may be grown, not accounting for inherent differences in phenological development between cultivars in the model and the presence of model deficits lead to inaccurate parameter estimates. To account for inherent differences between cultivars and to identify model deficits, we used a Bayesian multi-level approach to calibrate a phenology model (SPASS) to observations of silage maize grown across Germany between 2009 and 2017. We evaluated four multi-level models of increasing complexity, where we accounted for different combinations of ecological, weather, and year effects, as well as the hierarchical classification of cultivars nested within ripening groups of the maize species. We compared the calibration quality from this approach to the commonly used pooled approach in which none of these factors are considered. Our approach proved successful in improving calibration quality by incorporating the hierarchical classification of cultivars within ripening groups of maize. Our findings have implications for regional model calibration and data-gathering studies, since it emphasizes that ripening group and cultivar information is essential. Furthermore, we found that if this information is not available, at least weather, ecological regions and year effects should be taken into account. Our results can facilitate model improvement studies since we identified possible model limitations related to temperature effects in the reproductive (post-flowering) phase and to soil-moisture. We demonstrate that Bayesian multi-level calibration of a phenology model facilitates the incorporation of hierarchical dependencies and the identification of model limitations. Our approach can be extended to full crop models at different spatial scales.
Localized Leishmania major infection causes systemic iron deficiency that can be controlled by oral iron supplementation
Authors: Banerjee Sourav , Datta Rupak 
Published: June 2022

AbstractLeishmania major (L. major) and its related parasitic species infection causes human cutaneous leishmaniasis that results into disfiguring skin lesion. Although L. major infection has been found to alter macrophage iron homeostasis we have limited understanding on whether it can also manipulate the same at systemic level. In fact, localized L. major infection found to promote iron deficiency anemia in children by an unknown mechanism. To address these unresolved issues, Balb/c mouse were infected with L. major and iron status in different organs were monitored systematically with the development of cutaneous lesion. At week 10 post infection when there was maximum lesion development in the parasite infected left hind footpad, the iron content increased significantly in this tissue with the concomitant increase in parasite burden. L. major infection mediated iron accumulation in infected mouse footpad was found to be due to transferrin receptor upregulation and natural resistance-associated macrophage protein 1 (Nramp1) downregulation. Surge in iron level was found to be associated with the reduced hepatic iron storage that resulted increased serum iron. Limited iron storage in liver and bone-marrow of infected mice caused reduced hemoglobin level and production of deformed erythrocytes. Interestingly, L. major infected mice developed splenomegaly with significant upregulation of erythroid related genes. Importantly, oral iron supplementation post infection rescued the development of cutaneous lesion in infected mice. Together, our study unravelled a comprehensive mechanism behind developing iron deficiency anemia during cutaneous leishmaniasis and a novel therapeutic route of treating this infection by delivering iron.
Label-Free Hyperspectral Imaging and Deep-Learning Prediction of Retinal Amyloid β-Protein and Phosphorylated Tau
Authors: Du Xiaoxi , Koronyo Yosef , Mirzaei Nazanin , Yang Chengshuai , Fuchs Dieu-Trang , Black Keith L. , Koronyo-Hamaoui Maya , Gao Liang 
Published: June 2022

AbstractAlzheimer’s disease (AD) is a major risk for the aging population. The pathological hallmarks of AD—an abnormal deposition of amyloid β-protein (Aβ) and phosphorylated tau (pTau)—have been demonstrated in the retinas of AD patients, including in prodromal patients with mild cognitive impairment (MCI). Aβ pathology, especially the accumulation of the amyloidogenic 42-residue long alloform (Aβ42), is considered an early and specific sign of AD, and together with tauopathy, confirms AD diagnosis. To visualize retinal Aβ and pTau, state-of-the-art methods use fluorescence. However, administering contrast agents complicates the imaging procedure. To address this problem, we developed a label-free hyperspectral imaging method to detect the spectral signatures of Aβ42 and pS396-Tau and predicted their abundance in retinal cross sections. For the first time, we reported the spectral signature of pTau and demonstrated an accurate prediction of Aβ and pTau distribution powered by deep learning. We expect our finding will lay the groundwork for label-free detection of AD at its very earliest roots.Significance StatementThe pathological hallmarks of Alzheimer’s disease (AD), amyloid β-protein (Aβ) and hyperphosphorylated (p)Tau protein have been characterized by a hyperspectral camera in terms of spectral signatures. The unique optical properties of the hallmark proteins on the broad visible light range enable label-free and high-resolution detection and virtual staining of abnormal deposition in the retina tissue, which will lay the groundwork for AD early diagnosis and AD development quantification.
Extrinsic control of the early postnatal CA1 hippocampal circuits
Authors: Leprince Erwan , Dard Robin F. , Mortet Salomé , Filippi Caroline , Giorgi-Kurz Marie , Lenck-Santini Pierre-Pascal , Picardo Michel A. , Bocchio Marco , Baude Agnès , Cossart Rosa 
Published: June 2022

SUMMARYThe adult CA1 region of the hippocampus produces coordinated neuronal dynamics with minimal reliance on its extrinsic inputs. In contrast, the neonatal CA1 is tightly linked to externally-generated sensorimotor activity but the circuit mechanisms underlying early synchronous activity in CA1 remain unclear. Here, using a combination ofin vivoandex vivocircuit mapping, calcium imaging and electrophysiological recordings in mouse pups, we show that early dynamics in the ventro-intermediate CA1 are under the mixed influence of entorhinal (EC) and thalamic (VMT) inputs. Both VMT and EC can drive internally-generated synchronous eventsex vivo. However, movement-related population bursts detectedin vivoare exclusively driven by the EC. These differential effects on synchrony reflect the different intrahippocampal targets of these inputs. Hence, cortical and subcortical pathways act differently on the neonatal CA1, implying distinct contributions to the development of the hippocampal microcircuit and related cognitive maps.
Non-invasive auditory brainstem responses to FM sweeps in awake big brown bats
Authors: Simmons Andrea Megela , Tuninetti Amaro , Yeoh Brandon M. , Simmons James A. 
Published: June 2022

AbstractWe introduce two EEG techniques, one based on conventional monopolar electrodes and one based on a novel tripolar electrode, to record for the first time auditory brainstem responses (ABRs) from the scalp of unanesthetized, unrestrained big brown bats. Stimuli were frequency-modulated (FM) sweeps varying in sweep direction, sweep duration, and harmonic structure. As expected from previous invasive ABR recordings, upward-sweeping FM signals evoked larger amplitude responses (peak-to-trough amplitude in the latency range of 3-5 ms post-stimulus onset) than downward-sweeping FM signals. Scalp-recorded responses displayed amplitudelatency trading effects as expected from invasive recordings. These two findings validate the reliability of our noninvasive recording techniques. The feasibility of recording noninvasively in unanesthetized, unrestrained bats will energize future research uncovering electrophysological signatures of perceptual and cognitive processing of biosonar signals in these animals, and allows for better comparison with ABR data from echolocating cetaceans, where invasive experiments are heavily restricted. Because experiments can be repeated in the same animal over time without confounds of stress or anesthesia, our technique requires fewer captures of wild bats, thus helping to preserve natural populations and addressing the goal of reducing animal numbers used for research purposes.
A probabilistic successor representation for context-dependent prediction
Authors: Geerts Jesse P. , Gershman Samuel J. , Burgess Neil , Stachenfeld Kimberly L. 
Published: June 2022

AbstractThe different strategies that animals use for predicting reward are often classified as model-based or model-free reinforcement learning (RL) algorithms. Model-based RL involves explicit simulation the future to make decisions while model-free strategies rely on learning associations between stimuli and predicted reward by trial and error. An alternative, intermediate strategy for RL is based on the “successor representation” (SR), an encoding of environmental states in terms of predicted future states. A recent theoretical proposal suggests that the hippocampus encodes the SR in order to facilitate prediction of future reward. However, this proposal does not take into account how learning should adapt under uncertainty and switches of context. Here, we introduce a theory of learning SRs using prediction errors which includes optimally balancing uncertainty in new observations versus existing knowledge. We then generalise that approach to a multi-context setting, allowing the model to learn and maintain multiple task-specific SRs and infer which one to use at any moment based on the accuracy of its predictions. Thus, the context used for predictions can be determined by both the contents of the states themselves and the distribution of transitions between them. This probabilistic SR model captures animal behaviour in tasks which require contextual memory and generalisation, and unifies previous SR theory with hippocampal-dependent contextual decision making.
Doxorubicin induces prolonged DNA damage signal in cells overexpressing DEK isoform-2
Authors: Özçelik Emrah , Kalaycı Ahmet , Çelik Büşra , Avcı Açelya , Akyol Hasan , Baki Kılıç İrfan , Güzel Türkan , Çetin Metin , Tuzlakoğlu Öztürk Merve , Çalışkaner Zihni Onur , Tombaz Melike , Yoleri Dilan , Konu Özlen , Kandilci Ayten 
Published: June 2022

AbstractDEK has a short isoform (DEK isoform-2; DEK2) that lacks amino acid residues between 49-82. The full-length DEK (DEK isoform-1; DEK1) is ubiquitously expressed and plays a role in different cellular processes but whether DEK2 is involved in these processes remains elusive. We stably overexpressed DEK2 in human bone marrow stromal cell line HS-27A, in which endogenous DEKs were intact or suppressed via short hairpin RNA (sh-RNA). We have found that contrary to ectopic DEK1, DEK2 locates in the nucleus and nucleolus, causes persistent γH2AX signal upon doxorubicin treatment, and couldn’t functionally compensate for the loss of DEK1. In addition, DEK2 overexpressing cells were more sensitive to doxorubicin than DEK1-cells. Expressions of DEK1 and DEK2 in cell lines and primary tumors exhibit tissue specificity. DEK1 is upregulated in cancers of the colon, liver, and lung compared to normal tissues while both DEK1 and DEK2 are downregulated in subsets of kidney, prostate, and thyroid carcinomas. Interestingly, only DEK2 was downregulated in a subset of breast tumors suggesting that DEK2 can be modulated differently than DEK1 in specific cancers. In summary, our findings show distinct expression patterns and subcellular location and suggest non-overlapping functions between the two DEK isoforms.
Analysis of SMAD1/5 target genes in a sea anemone reveals ZSWIM4-6 as a novel BMP signaling modulator
Authors: Knabl Paul , Schauer Alexandra , Pomreinke Autumn Penecilla , Zimmermann Bob , Rogers Katherine W. , Müller Patrick , Genikhovich Grigory 
Published: June 2022

AbstractBMP signaling has a conserved function in patterning the dorsal-ventral body axis in Bilateria and the directive axis in anthozoan cnidarians. So far, cnidarian studies have focused on the role of different BMP signaling network components in regulating pSMAD1/5 gradient formation. Much less is known about the target genes downstream of BMP signaling. To address this, we generated a genome-wide list of direct pSMAD1/5 target genes in the anthozoan Nematostella vectensis, several of which were conserved in Drosophila and Xenopus. Our ChIP-Seq analysis revealed that many of the regulatory molecules with documented bilaterally symmetric expression in Nematostella are directly controlled by BMP signaling. Among the so far uncharacterized BMP-dependent transcription factors and signaling molecules we identified several, whose bilaterally symmetric expression may be indicative of their involvement in secondary axis patterning. One of these molecules, zswim4-6, encodes a novel nuclear modulator of the pSMAD1/5 gradient potentially promoting BMP-dependent gene repression. Strikingly, overexpression of the zebrafish homologue zswim5 suggests that its effect on the pSMAD1/5 gradient is conserved between anthozoan Cnidaria and Bilateria.