bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceived facilitators and barriers to healthy dietary behaviour in adults with type 2 diabetes mellitus in Kenya: a qualitative study
Authors: Mokaya Moses , Saruni Eddah , Kyallo Florence , Vangoitsenhoven Roman , Matthys Christophe
Published: October 2022

Objective:

This study aimed to explore the facilitators and barriers to healthy dietary behaviour in adults with type 2 diabetes mellitus (T2DM) in Kenya.

Design:

A qualitative descriptive design using telephone interviews was applied. An interview guide was developed through a modified theoretical framework.

Setting:

This study was conducted in selected hospitals in Nakuru County, located in west-central Kenya.

Participants:

A two-step sampling strategy was used to select hospitals and study participants. Adult participants aged 30 to 85 years, with T2DM from six hospitals were selected based on their ability to openly elaborate on the theme of dietary behaviour.

Results:

Thirty respondents were interviewed (mean age 62 years; 43·3 % females). The average duration of the interviews was 32:02 min (sd 17·07). The highest-ranking internal facilitators of healthy dietary behaviour were knowledge of healthy food choices, gardening, self-efficacy, food preparation skills and eating at home. External facilitators included inaccurate beliefs and information on food and diet, education by healthcare workers, food availability, proximity to food selling points and family support. Internal barriers included tastes and preferences, health conditions barring intake of certain foods, and random eating of unhealthy foods. External barriers included socio-economic factors, seasonal unavailability of fruits and food safety concerns.

Conclusions:

Facilitators and barriers to healthy dietary behaviour among Kenyan adults with T2DM are related to food literacy and include selection, preparation and eating. Interventions to enhance healthy dietary behaviour should target context-specific knowledge, skills and self-efficacy.
Quality of life, anxiety, depression, and distress in patients with advanced and metastatic lung cancer
Authors: Gonzalez-Ling Ana , Galindo Vázquez Oscar , Espinoza Bello Marcos , Robles Rebeca , Rascón-Gasca María Luisa , Lara-Mejía Luis , Heredia David , Arrieta Oscar
Published: October 2022

Objective

Lung cancer (LC) patients have shown a predisposition for developing emotional and physical symptoms, with detrimental effects on the quality of life (QoL). This study evaluates the bidirectional relationship between main psychological disorders and clinical/sociodemographic factors with the QoL.

Methods

In this observational cross-sectional study, patients with a confirmed LC diagnosis from February 2015 to March 2018 were eligible for this study. Each participant completed screening instruments of anxiety, depression, distress, and QoL assessment. Other relevant clinical data were extracted from electronic health records. Then comparisons, correlations, and logistic regression analyses were performed.

Results

Two hundred and four cases were eligible; of them, the median age was 61 (24–84) years, most had clinical stage IV (95%), and most were under first-line therapy (53%). Concerning psychological status, 46% had symptoms of emotional distress, 35% anxiety, and 31% depression. Patients with psychological disorders experienced a worse global QoL than those without psychological impairment (p < 0.001). Increased financial issues and physical symptoms, combined with lower functioning, were also significantly associated with anxiety, depression, and distress. In the multivariate analysis, female sex and emotional distress were positively associated with an increased risk of depression; likewise, female sex, low social functioning, insomnia, and emotional distress were associated with anxiety.

Conclusions

Emotional symptoms and QoL had a significant bidirectional effect on this study; this underscores the necessity to identify and treat anxiety, depression, and distress to improve psychological well-being and the QoL in LC patients.
Validation of the Spanish Version of the Generic Conspiracist Beliefs Scale
Authors: Fasce Angelo , Avendaño Diego , Dagnall Neil , Denovan Andrew , Escolà-Gascón Álex
Published: October 2022

Theorists acknowledge that conspiracy beliefs represent an established psychological construct. The study of conspiracy beliefs is important because allied ideation potentially influences everyday attitudes and behaviors across a range of domains (i.e., cognitive, social, cross-cultural, and political psychology). In this article, we analyze the internal structure and construct validity of the Spanish adaptation of the Generic Conspiracist Beliefs Scale (GCBS). Correlational and confirmatory factor analyses using an international sample of 732 Spanish-speakers revealed a five-factor structure equivalent to the original instrument. Convergent validity was demonstrated using educational level, political orientation, need for uniqueness, and four social axioms (social cynicism, religiosity, reward for application, and fate control). In comparison to two English samples (N = 794 and N = 421), the adaptation demonstrated satisfactory, although restricted, levels of invariance. Accordingly, findings support the use of this translated form of the GCBS with Spanish speakers.
Improved High‐Resolution Bathymetry Map of Tamu Massif and Southern Shatsky Rise and Its Geologic Implications
Authors: Thoram S. , Sager W. W. , Reed W. , Nakanishi M. , Zhang J.
Published: October 2022

The formation and geology of oceanic plateaus are incompletely understood, in part because geophysical data are sparse and of low density. This paper presents an improved high‐resolution bathymetry map for southern Shatsky Rise, by combining newly acquired multibeam bathymetry data from several cruises and by filling in gaps in multibeam coverage with the SRTM15+ global bathymetry model. This map provides important insights on the evolution of Shatsky Rise from plateau forming, to post‐plateau secondary volcanism, to sedimentation, erosion, and sedimentary mass wasting. Tamu Massif is segmented by several subdued bathymetric troughs that divide the massif flanks into smaller rises. The segmentation pattern suggests Tamu Massif was built by a series of eruptions along a jumping triple junction. The distribution of secondary volcanic cones is non‐uniform, with most occurring on the southern and eastern flanks. Most of these secondary cones occur as short chains that parallel nearby magnetic lineations, suggesting control by spreading ridge parallel faults. These results suggest the evolution of Shatsky Rise was largely controlled by spreading ridges during its active volcanic phase. Numerous escarpments were identified around the plateau, a majority of which parallel bathymetry contours, suggesting these features developed because of differential subsidence of the rise massifs. The map reveals widespread mass wasting and downslope sediment movement, shifting sediment distribution and changing the surface morphology. Improved topography improves our understanding of the evolution of Shatsky Rise and emphasizes the importance of bathymetry data in deciphering the geodynamic evolution of large igneous provinces.
Comprehensive Assessment of Seasonally Frozen Ground Changes in the Northern Hemisphere Based on Observations
Authors: Chen Cong , Peng Xiaoqing , Frauenfeld Oliver W. , Zhao Yaohua , Yang Guangshang , Tian Weiwei , Li Xuanjia , Du Ran , Li Xiaodong
Published: October 2022

Seasonally frozen ground (SFG) in the Northern Hemisphere (NH) plays a significant role in the earth system via changes in the freeze‐thaw cycle. Previous studies primarily focus on permafrost; however, the SFG response to climate change on a hemispheric scale is uncertain due to a lack of observations. We rectify this with a newly assembled comprehensive database of 1,220 stations with daily observations. To quantify the spatiotemporal characteristics of SFG in response to climate change, we calculate eight variables with these observations: the first date of soil freeze (FFD), freezing duration (FDR), maximum freeze depth (MFD), the date of maximum freeze depth (MFDD), the last date of soil thaw (TLD), thawing duration (TDR), freeze‐thaw duration (FTDR), and actual number of freezing days (AD). During the variables' common 1986–2005 period, MFD decreased 8.9 cm (9% change). FFD was later by 5.3 days (2% change), MFDD and TLD were earlier by 14.5 days (27% change) and 24.7 days (22% change), respectively, and FDR and TDR decreased by 9 days (11% change) and 4.6 days (10% change). FTDR and AD decreased 18.1 days (14% change) and 12.1 days (10% change), respectively. The spatial pattern of freeze‐thaw variables depends on latitude and elevation, and varies by climatic zone: FTDR increases, going from the warm temperate climate, to the arid climate, and the snow and polar climates. The variability in freeze‐thaw changes is mainly driven by air temperature and latitude, while precipitation, soil moisture, snow depth, and elevation are relatively insignificant at the hemispheric scale.
Planetary Core‐Style Rotating Convective Flows in Paraboloidal Laboratory Experiments
Authors: Lonner Taylor L. , Aggarwal Ashna , Aurnou Jonathan M.
Published: October 2022

Turbulent convection in a planet's outer core is simulated here using a thermally‐driven, free surface paraboloidal laboratory annulus. We show that the rapidly rotating convection dynamics in free‐surface paraboloidal annuli are similar those in planetary spherical shell geometries. Three experimental cases are carried out, respectively, at 35 revolutions per minute (rpm), 50 and 60 rpm. Thermal Rossby waves are detected in full disk thermographic images of the fluid's free surface. Ultrasonic flow velocity measurements reveal the presence of multiple azimuthal (zonal) jets, with successively more jets forming in higher rotation rate cases. The jets' cylindrical radial extent is well approximated by the Rhines scale. Over time, the zonal jets migrate to larger radial position with migration rates in good agreement with prior theoretical estimates. Our results suggest that planetary core rotating convection will be comprised of flow structures found in other turbulent geophysical fluid dynamical systems: convective turbulence dominates the small‐scale flow field, and also act to flux energy into larger‐scale, slowly evolving zonal flow structures. How the ambient magnetic fields in planetary core settings affect such turbulent flows remains an open question.
IFT140+/K14+ cells function as stem/progenitor cells in salivary glands
Authors: Zhang Xueming , Zhou Ji , Wang Xinyu , Geng Jiangyu , Chen Yubei , Sun Yao
Published: October 2022

Stem/progenitor cells are important for salivary gland development, homeostasis maintenance, and regeneration following injury. Keratin-14+(K14+) cells have been recognized as bona fide salivary gland stem/progenitor cells. However, K14 is also expressed in terminally differentiated myoepithelial cells; therefore, more accurate molecular markers for identifying salivary stem/progenitor cells are required. The intraflagellar transport (IFT) protein IFT140 is a core component of the IFT system that functions in signaling transduction through the primary cilia. It is reportedly expressed in mesenchymal stem cells and plays a role in bone formation. In this study, we demonstrated that IFT140 was intensively expressed in K14+stem/progenitor cells during the developmental period and early regeneration stage following ligation-induced injuries in murine submandibular glands. In addition, we demonstrated that IFT140+/ K14+could self-renew and differentiate into granular duct cells at the developmental stage in vivo. The conditional deletion ofIft140from K14+cells caused abnormal epithelial structure and function during salivary gland development and inhibited regeneration. IFT140 partly coordinated the function of K14+stem/progenitor cells by modulating ciliary membrane trafficking. Our investigation identified a combined marker, IFT140+/K14+, for salivary gland stem/progenitor cells and elucidated the essential role of IFT140 and cilia in regulating salivary stem/progenitor cell differentiation and gland regeneration.
Fecal microbiome alterations in treatment-naive de novo Parkinson’s disease
Authors: Boertien Jeffrey M. , Murtomäki Kirsi , Pereira Pedro A. B. , van der Zee Sygrid , Mertsalmi Tuomas H. , Levo Reeta , Nojonen Tanja , Mäkinen Elina , Jaakkola Elina , Laine Pia , Paulin Lars , Pekkonen Eero , Kaasinen Valtteri , Auvinen Petri , Scheperjans Filip , van Laar Teus ,   PPNN Study Group, Verwey N. A. , van Harten B. , Portman A. T. , Langedijk M. J. H. , Oomes P. G. , Jansen B. J. A. M. , van Wieren T. , van den Bogaard S. J. A. , van Steenbergen W. , Duyff R. , van Amerongen J. P. , Fransen P. S. S. , Polman S. K. L. , Zwartbol R. T. , van Kesteren M. E. , Braakhekke J. P. , Trip J. , Koops L. , de Langen C. J. , de Jong G. , Hartono J. E. S. , Ybema H. , Bartels A. L. , Reesink F. E. , Postma A. G. , Vonk G. J. H. , Oen J. M. T. H. , Brinkman M. J. , Mondria T. , Holscher R. S. , van der Meulen A. A. E. , Rutgers A. W. F. , Boekestein W. A. , Teune L. K. , Orsel P. J. L. , Hoogendijk J. E. , van Laar T.
Published: October 2022

Gut microbiota alterations in Parkinson’s disease (PD) have been found in several studies and are suggested to contribute to the pathogenesis of PD. However, previous results could not be adequately adjusted for a potential confounding effect of PD medication and disease duration, as almost all PD participants were already using dopaminergic medication and were included several years after diagnosis. Here, the gut microbiome composition of treatment-naive de novo PD subjects was assessed compared to healthy controls (HC) in two large independent case-control cohorts (n = 136 and 56 PD, n = 85 and 87 HC), using 16S-sequencing of fecal samples. Relevant variables such as technical batches, diet and constipation were assessed for their potential effects. Overall gut microbiome composition differed between PD and HC in both cohorts, suggesting gut microbiome alterations are already present in de novo PD subjects at the time of diagnosis, without the possible confounding effect of dopaminergic medication. Although no differentially abundant taxon could be replicated in both cohorts, multiple short chain fatty acids (SCFA) producing taxa were decreased in PD in both cohorts. In particular, several taxa belonging to the family Lachnospiraceae were decreased in abundance. Fewer taxonomic differences were found compared to previous studies, indicating smaller effect sizes in de novo PD.
DNA methylation levels of RELN promoter region in ultra-high risk, first episode and chronic schizophrenia cohorts of schizophrenia
Authors: Kho Sok-Hong , Yee Jie Yin , Puang Shu Juan , Han Luke , Chiang Christine , Rapisarda Attilio , Goh Wilson Wen Bin , Lee Jimmy , Sng Judy Chia Ghee
Published: October 2022

The essential role of the Reelin gene (RELN) during brain development makes it a prominent candidate in human epigenetic studies of Schizophrenia. Previous literature has reported differing levels of DNA methylation (DNAm) in patients with psychosis. Therefore, this study aimed to (1) examine and compare RELN DNAm levels in subjects at different stages of psychosis cross-sectionally, (2) analyse the effect of antipsychotics (AP) on DNAm, and (3) evaluate the effectiveness and applicability of RELN promoter DNAm as a possible biological-based marker for symptom severity in psychosis.. The study cohort consisted of 56 healthy controls, 87 ultra-high risk (UHR) individuals, 26 first-episode (FE) psychosis individuals and 30 chronic schizophrenia (CS) individuals. The Positive and Negative Syndrome Scale (PANSS) was used to assess Schizophrenia severity. After pyrosequencing selected CpG sites of peripheral blood, the Average mean DNAm levels were compared amongst the 4 subgroups. Our results showed differing levels of DNAm, with UHR having the lowest (7.72 ± 0.19) while the CS had the highest levels (HC: 8.78 ± 0.35; FE: 7.75 ± 0.37; CS: 8.82 ± 0.48). Significantly higher Average mean DNAm levels were found in CS subjects on AP (9.12 ± 0.61) compared to UHR without medication (UHR(−)) (7.39 ± 0.18). A significant association was also observed between the Average mean DNAm of FE and PANSS Negative symptom factor (R2 = 0.237, ß = −0.401, *p = 0.033). In conclusion, our findings suggested different levels of DNAm for subjects at different stages of psychosis. Those subjects that took AP have different DNAm levels. There were significant associations between FE DNAm and Negative PANSS scores. With more future experiments and on larger cohorts, there may be potential use of DNAm of the RELN gene as one of the genes for the biological-based marker for symptom severity in psychosis.
Fast and scalable search of whole-slide images via self-supervised deep learning
Authors: Chen Chengkuan , Lu Ming Y. , Williamson Drew F. K. , Chen Tiffany Y. , Schaumberg Andrew J. , Mahmood Faisal
Published: October 2022

The adoption of digital pathology has enabled the curation of large repositories of gigapixel whole-slide images (WSIs). Computationally identifying WSIs with similar morphologic features within large repositories without requiring supervised training can have significant applications. However, the retrieval speeds of algorithms for searching similar WSIs often scale with the repository size, which limits their clinical and research potential. Here we show that self-supervised deep learning can be leveraged to search for and retrieve WSIs at speeds that are independent of repository size. The algorithm, which we named SISH (for self-supervised image search for histology) and provide as an open-source package, requires only slide-level annotations for training, encodes WSIs into meaningful discrete latent representations and leverages a tree data structure for fast searching followed by an uncertainty-based ranking algorithm for WSI retrieval. We evaluated SISH on multiple tasks (including retrieval tasks based on tissue-patch queries) and on datasets spanning over 22,000 patient cases and 56 disease subtypes. SISH can also be used to aid the diagnosis of rare cancer types for which the number of available WSIs is often insufficient to train supervised deep-learning models.
Health effects associated with vegetable consumption: a Burden of Proof study
Authors: Stanaway Jeffrey D. , Afshin Ashkan , Ashbaugh Charlie , Bisignano Catherine , Brauer Michael , Ferrara Giannina , Garcia Vanessa , Haile Demewoz , Hay Simon I. , He Jiawei , Iannucci Vincent , Lescinsky Haley , Mullany Erin C. , Parent Marie C. , Serfes Audrey L. , Sorensen Reed J. D. , Aravkin Aleksandr Y. , Zheng Peng , Murray Christopher J. L.
Published: October 2022

Previous research suggests a protective effect of vegetable consumption against chronic disease, but the quality of evidence underlying those findings remains uncertain. We applied a Bayesian meta-regression tool to estimate the mean risk function and quantify the quality of evidence for associations between vegetable consumption and ischemic heart disease (IHD), ischemic stroke, hemorrhagic stroke, type 2 diabetes and esophageal cancer. Increasing from no vegetable consumption to the theoretical minimum risk exposure level (306–372 g daily) was associated with a 23.2% decline (95% uncertainty interval, including between-study heterogeneity: 16.4–29.4) in ischemic stroke risk; a 22.9% (13.6–31.3) decline in IHD risk; a 15.9% (1.7–28.1) decline in hemorrhagic stroke risk; a 28.5% (−0.02–51.4) decline in esophageal cancer risk; and a 26.1% (−3.6–48.3) decline in type 2 diabetes risk. We found statistically significant protective effects of vegetable consumption for ischemic stroke (three stars), IHD (two stars), hemorrhagic stroke (two stars) and esophageal cancer (two stars). Including between-study heterogeneity, we did not detect a significant association with type 2 diabetes, corresponding to a one-star rating. Although current evidence supports increased efforts and policies to promote vegetable consumption, remaining uncertainties suggest the need for continued research.
Adult-born dentate granule cells promote hippocampal population sparsity
Authors: McHugh Stephen B. , Lopes-dos-Santos Vítor , Gava Giuseppe P. , Hartwich Katja , Tam Shu K. E. , Bannerman David M. , Dupret David
Published: October 2022

The dentate gyrus (DG) gates neocortical information flow to the hippocampus. Intriguingly, the DG also produces adult-born dentate granule cells (abDGCs) throughout the lifespan, but their contribution to downstream firing dynamics remains unclear. Here, we show that abDGCs promote sparser hippocampal population spiking during mnemonic processing of novel stimuli. By combining triple-(DG-CA3-CA1) ensemble recordings and optogenetic interventions in behaving mice, we show that abDGCs constitute a subset of high-firing-rate neurons with enhanced activity responses to novelty and strong modulation by theta oscillations. Selectively activating abDGCs in their 4–7-week post-birth period increases sparsity of hippocampal population patterns, whereas suppressing abDGCs reduces this sparsity, increases principal cell firing rates and impairs novel object recognition with reduced dimensionality of the network firing structure, without affecting single-neuron spatial representations. We propose that adult-born granule cells transiently support sparser hippocampal population activity structure for higher-dimensional responses relevant to effective mnemonic information processing.
U(VI) removal from diluted aqueous systems by sorption–flotation
Authors: Constantin Carolina , Popescu Ioana-Carmen , Oprea Ovidiu , Stoica Ligia
Published: October 2022

The legacies of past uranium mining and milling activities for nuclear fuel fabrication continue to be a cause of concern and require assessment and remedial action for researchers worldwide. The discharge of uranium contaminated water into the environment is a matter of regulation (World Health Organization, WHO—15 μg/L, Romanian Legislation, RO—21 μg/L), environment and health. Therefore, various removal technologies of U(VI) from diluted aqueous solutions include chemical precipitation, ion exchange, adsorption, immobilization on zero-valent iron nanoparticles, etc. have been extensively applied. Our previous research has studied the removal of U(VI) from diluted aqueous systems such as mine waters using Fe0-based nanomaterials synthesized in the laboratory (NMS) (Crane et al. in Water Res 45:2391–2942, 2011). The carbonate rich aqueous system was treated with NMS to remove U(VI). It was observed that after half an hour of reacting time only about 50% was removed due to its high tendency to form stable soluble carbonated complexes. Considering that, the present article aims to investigate the Sorption/Flotation technique, by using a sorbent generated in situ Fe2O3· nH2O and sodium oleate surfactant to remove U(VI) from diluted aqueous systems and to update the knowledge on the mechanism of process. In order to determine the removal efficiency of U(VI), the influencing factors were studied: pH, sorbent dose, surfactant concentration, contact time, stirring rate, the U(VI) concentration, air pressure in pressurized water recipient, and the effect of some accompanying heavy metals ions (Cu(II), Cr(VI), and Mo(VI)). The removal efficiency (%R) was monitored and its maximum values allowed to establish the optimal separation parameters (the established process parameters), which were validated on real mine water samples (MW). High U (VI) removal efficiencies %R > 98% were obtained. The Sorption/ Flotation technique was applied to remove U(VI) from two types of real mine water samples, namely ”simple” and ”pre-treated with NMS”, respectively. For the mine water samples pre-treated with NMS, it worked in two variants: with and without pH correction. For pH range = 7.5–9.5, molar ratios [U(VI)] : [Fe(III)] = 1 : 75, [U(VI)] : [NaOL] = 1 : 1 × 10–2, contact time 30 min., stirring speed 250 RPM, initial concentration of U(VI) 10 mg·L−1, air pressure in pressurized water recipient p = 4 × 105 N·m−2 is obtained %R > 98%. It has been found that Sorption / Flotation can function with good %R values as a stand—alone operation or in tandem with NMS pre-treatment of mine water and pH adjustment proved to be highly efficiency (CU(VI) < 1·10–3 mg·L−1).
Gut microbiome insights from 16S rRNA analysis of 17-year periodical cicadas (Hemiptera: Magicicada spp.) Broods II, VI, and X
Authors: Brumfield Kyle D. , Raupp Michael J. , Haji Diler , Simon Chris , Graf Joerg , Cooley John R. , Janton Susan T. , Meister Russell C. , Huq Anwar , Colwell Rita R. , Hasan Nur A.
Published: October 2022

Periodical cicadas (Hemiptera: Magicicada) have coevolved with obligate bacteriome-inhabiting microbial symbionts, yet little is known about gut microbial symbiont composition or differences in composition among allochronic Magicicada broods (year classes) which emerge parapatrically or allopatrically in the eastern United States. Here, 16S rRNA amplicon sequencing was performed to determine gut bacterial community profiles of three periodical broods, including II (Connecticut and Virginia, 2013), VI (North Carolina, 2017), and X (Maryland, 2021, and an early emerging nymph collected in Ohio, 2017). Results showed similarities among all nymphal gut microbiomes and between morphologically distinct 17-year Magicicada, namely Magicicada septendecim (Broods II and VI) and 17-year Magicicada cassini (Brood X) providing evidence of a core microbiome, distinct from the microbiome of burrow soil inhabited by the nymphs. Generally, phyla Bacteroidetes [Bacteroidota] (> 50% relative abundance), Actinobacteria [Actinomycetota], or Proteobacteria [Pseudomonadota] represented the core. Acidobacteria and genera Cupriavidus, Mesorhizobium, and Delftia were prevalent in nymphs but less frequent in adults. The primary obligate endosymbiont, Sulcia (Bacteroidetes), was dominant amongst core genera detected. Chryseobacterium were common in Broods VI and X. Chitinophaga, Arthrobacter, and Renibacterium were common in Brood X, and Pedobacter were common to nymphs of Broods II and VI. Further taxonomic assignment of unclassified Alphaproteobacteria sequencing reads allowed for detection of multiple copies of the Hodgkinia 16S rRNA gene, distinguishable as separate operational taxonomic units present simultaneously. As major emergences of the broods examined here occur at 17-year intervals, this study will provide a valuable comparative baseline in this era of a changing climate.
Enterotypes in asthenospermia patients with obesity
Authors: Jiao Jiao , Xu Peng , Wang Xiaobin , Xing Ze , Dong Sitong , Li Gaoyu , Yao Xinrui , Guo Renhao , Feng Tao , Yao Weifan , Pan Bochen , Zhu Xuan , Wang Xiuxia
Published: October 2022

The essence of enterotypes is stratifying the entire human gut microbiome, which modulates the association between diet and disease risk. A study was designed at the Center of Reproductive Medicine, Shengjing Hospital of China Medical University and Jinghua Hospital of Shenyang. Prevotella and Bacteroides were analyzed in 407 samples of stool, including 178 men with enterotype B (61 normal, 117 overweight/obese) and 229 men with enterotype P (74 normal, 155 overweight/obese). The ratio between Prevotella and Bacteroides abundance, P/B, was used as a simplified way to distinguish the predominant enterotype. In enterotype P group (P/B ≥ 0.01), obesity was a risk factor for a reduced rate of forward progressive sperm motility (odds ratio [OR] 3.350; 95% confidence interval [CI] 1.881–5.966; P < 0.001), and a reduced rate of total sperm motility (OR 4.298; 95% CI 2.365–7.809; P < 0.001). Obesity was also an independent risk factor (OR 3.131; 95% CI 1.749–5.607; P < 0.001) after adjusting follicle-stimulating hormone. In enterotype P, body mass index, as a diagnostic indicator of a reduced rate of forward progressive sperm motility and a decreased rate of decreased total sperm motility, had AUC values of 0.627 (P = 0.001) and 0.675 (P < 0.0001), respectively, which were significantly higher than the predicted values in all patients. However, in enterotype B group (P < 0.01), obesity was not a risk factor for asthenospermia, where no significant difference between obesity and sperm quality parameters was observed. This study is tried to introduce enterotypes as a population-based individualized classification index to investigate the correlation between BMI and asthenospermia. In our study, overweight/obese men with enterotype P were found to have poorer sperm quality. however, sperm quality was not associated with overweight/obese in men with enterotype B. Thereof, BMI is a risk factor for asthenospermia only in men with enterotype P, but not in men with enterotype B.
Epidermal growth factor receptor cascade prioritizes the maximization of signal transduction
Authors: Kiso-Farnè Kaori , Tsuruyama Tatsuaki
Published: October 2022

Many studies have been performed to quantify cell signaling. Cell signaling molecules are phosphorylated in response to extracellular stimuli, with the phosphorylation sequence forming a signal cascade. The information gain during a signal event is given by the logarithm of the phosphorylation molecule ratio. The average information gain can be regarded as the signal transduction quantity (ST), which is identical to the Kullback–Leibler divergence (KLD), a relative entropy. We previously reported that if the total ST value in a given signal cascade is maximized, the ST rate (STR) of each signaling molecule per signal duration (min) approaches a constant value. To experimentally verify this theoretical conclusion, we measured the STR of the epidermal growth factor (EGF)-related cascade in A431 skin cancer cells following stimulation with EGF using antibody microarrays against phosphorylated signal molecules. The results were consistent with those from the theoretical analysis. Thus, signaling transduction systems may adopt a strategy that prioritizes the maximization of ST. Furthermore, signal molecules with similar STRs may form a signal cascade. In conclusion, ST and STR are promising properties for quantitative analysis of signal transduction.
Identifying a novel role for the master regulator Tal1 in the Endothelial to Hematopoietic Transition
Authors: Serina Secanechia Yasmin Natalia , Bergiers Isabelle , Rogon Matt , Arnold Christian , Descostes Nicolas , Le Stephanie , López-Anguita Natalia , Ganter Kerstin , Kapsali Chrysi , Bouilleau Lea , Gut Aaron , Uzuotaite Auguste , Aliyeva Ayshan , Zaugg Judith B. , Lancrin Christophe
Published: October 2022

Progress in the generation of Hematopoietic Stem and Progenitor Cells (HSPCs) in vitro and ex vivo has been built on the knowledge of developmental hematopoiesis, underscoring the importance of understanding this process. HSPCs emerge within the embryonic vasculature through an Endothelial-to-Hematopoietic Transition (EHT). The transcriptional regulatorTal1exerts essential functions in the earliest stages of blood development, but is considered dispensable for the EHT. Nevertheless,Tal1is expressed with its binding partnerLmo2and it homologousLyl1in endothelial and transitioning cells at the time of EHT. Here, we investigated the function of these genes using a mouse embryonic-stem cell (mESC)-based differentiation system to model hematopoietic development. We showed for the first time that the expression of TAL1 in endothelial cells is crucial to ensure the efficiency of the EHT process and a sustained hematopoietic output. Our findings uncover an important function ofTal1during the EHT, thus filling the current gap in the knowledge of the role of this master gene throughout the whole process of hematopoietic development.
Deconstructing the driving factors of land development intensity from multi-scale in differentiated functional zones
Authors: Yin Yue , Zhou Kan , Chen Yufan
Published: October 2022

Land development intensity (LDI) is an important indicator of how much human exploitation of land resources. Against the background of rapid urbanization and industrialization, in order to curb the over-occupation of agricultural and ecological space by urbanized space, China has proposed the Major Functional Zoning Planning (MFZP) as a new spatial governance model, which attempts to implement differentiated LDI control according to the functional positioning of different regions. To observe the spatio-temporal evolution and drivers of LDI in the first five years since the implementation of the MFZP, we chose the Yangtze River Delta, the most urbanized region in China, as a case area. The multi-scale distribution pattern of LDI was analyzed by combining macro and micro scales, and a new spatial measurement method integrating global and local regression models was developed to quantitatively deconstruct the natural-human drivers of LDI in different functional zones. Results demonstrate that LDI decreases in a gradient of the urbanized zone (UZ) > main agricultural production zone (MAPZ) > key ecological function zone (KEFZ). In the UZ, LDI is influenced by natural-human multi factors, e.g., terrain conditions (SLP), proportion of cultivated land area (PCL), proportion of ecologically important area (EID), population urbanization rate (PUR), GDP per capita (PGDP), fixed asset investment size per land (FAI) and fiscal expenditure as a percentage of GDP (FD). The LDI in the MAPZ is mainly affected by the facilitating role of PCL, EID, FAI, and the prominent role of FD, while that in the KEFZ is mainly inhibited by SLP, EID, and driven by the PGDP. The diverse drivers of LDI in different functional zones remind us to implement differentiated spatial control according to functional positioning and to adopt refined policy tools of zoning and classification to ensure that land resources within each type of functional zone can be used sustainably.
Feasibility of ApoC1 serum levels as tumor biomarker in glioblastoma patients: a pilot study
Authors: Hilbert Michelle , Kuzman Peter , Mueller Wolf C. , Meixensberger Jürgen , Nestler Ulf
Published: October 2022

Apolipoprotein C1 (ApoC1) has been detected immunohistochemically in glioblastoma tissue, probably expressed by activated monocytes and microglia. The present study was conceived to determine whether the amount of intratumoral ApoC1 expression leads to measurable changes of serum levels after glioblastoma resection or during recurrence. 176 blood samples from 70 glioblastoma patients were collected perioperatively and during subsequent therapy. ApoC1 serum levels were determined using an enzyme linked immunosorbent assay (ELISA). High absorption values due to lipemic or hemolytic serum were removed from the final dataset using a stem and leaf plot. Samples were grouped according to the treatment stage to compare mean ApoC1 serum levels. The number of patients with falling or increasing perioperative values was assessed. 167 ApoC1 serum values from 68 glioblastoma patients were amenable to statistical evaluation. Mean ApoC1 serum level was 91.9 µg/ml (n = 167, sd = 36.0). In samples from patients undergoing first glioblastoma resection, the mean preoperative value was significantly higher (94.8 µg/ml, n = 37, sd = 29.5) than after surgery (77.4 µg/ml, n = 41, sd = 23.2, p = 0.009). Individually, falling ApoC1 levels were detected in 25 and rising levels in 9 patients (p = 0.0061). Single absolute serum levels of ApoC1 do not allow an estimation of glioblastoma activity or tumor response. Although pathophysiologically of interest, ApoC1 serum levels did not qualify as a potential biomarker in glioblastoma management. Our results do not seem to encourage larger, multicenter studies.
Efficacy of COVID-HIGIV in animal models of SARS-CoV-2 infection
Authors: Jha Aruni , Barker Douglas , Lew Jocelyne , Manoharan Vinoth , van Kessel Jill , Haupt Robert , Toth Derek , Frieman Matthew , Falzarano Darryl , Kodihalli Shantha
Published: October 2022

In late 2019 the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged in China and quickly spread into a worldwide pandemic. It has caused millions of hospitalizations and deaths, despite the use of COVID-19 vaccines. Convalescent plasma and monoclonal antibodies emerged as major therapeutic options for treatment of COVID-19. We have developed an anti-SARS-CoV-2 immunoglobulin intravenous (Human) (COVID-HIGIV), a potential improvement from using convalescent plasma. In this report the efficacy of COVID-HIGIV was evaluated in hamster and mouse models of SARS-CoV-2 infection. COVID-HIGIV treatment in both mice and hamsters significantly reduced the viral load in the lungs. Among COVID-HIGIV treated animals, infection-related body weight loss was reduced and the animals regained their baseline body weight faster than the PBS controls. In hamsters, COVID-HIGIV treatment reduced infection-associated lung pathology including lung inflammation, and pneumocyte hypertrophy in the lungs. These results support ongoing trials for outpatient treatment with COVID-HIGIV for safety and efficacy evaluation (NCT04910269, NCT04546581).
Metagenomic DNA sequencing to quantify Mycobacterium tuberculosis DNA and diagnose tuberculosis
Authors: Chang Adrienne , Mzava Omary , Djomnang Liz-Audrey Kounatse , Lenz Joan Sesing , Burnham Philip , Kaplinsky Peter , Andama Alfred , Connelly John , Bachman Christine M. , Cattamanchi Adithya , Steadman Amy , De Vlaminck Iwijn
Published: October 2022

Tuberculosis (TB) remains a significant cause of mortality worldwide. Metagenomic next-generation sequencing has the potential to reveal biomarkers of active disease, identify coinfection, and improve detection for sputum-scarce or culture-negative cases. We conducted a large-scale comparative study of 428 plasma, urine, and oral swab samples from 334 individuals from TB endemic and non-endemic regions to evaluate the utility of a shotgun metagenomic DNA sequencing assay for tuberculosis diagnosis. We found that the composition of the control population had a strong impact on the measured performance of the diagnostic test: the use of a control population composed of individuals from a TB non-endemic region led to a test with nearly 100% specificity and sensitivity, whereas a control group composed of individuals from TB endemic regions exhibited a high background of nontuberculous mycobacterial DNA, limiting the diagnostic performance of the test. Using mathematical modeling and quantitative comparisons to matched qPCR data, we found that the burden of Mycobacterium tuberculosis DNA constitutes a very small fraction (0.04 or less) of the total abundance of DNA originating from mycobacteria in samples from TB endemic regions. Our findings suggest that the utility of a minimally invasive metagenomic sequencing assay for pulmonary tuberculosis diagnostics is limited by the low burden of M. tuberculosis and an overwhelming biological background of nontuberculous mycobacterial DNA.
Role of income and government responsiveness in reducing the death toll from floods in Indian states
Authors: Parida Yashobanta , Roy Chowdhury Joyita , Saini Swati , Dash Devi Prasad
Published: October 2022

Floods are the most commonly occurring natural disasters in India due to India’s unique geographical location and socioeconomic conditions. Frequent flooding causes enormous loss of human lives and damage crops and public utilities. Furthermore, floods adversely affect economic development and increase the government's financial burden by increasing spending on various disaster mitigation measures. Recent empirical literature based on cross-national comparisons shows that disaster fatalities and damages are monotonically decreasing in per capita income. We challenge this view on the monotonic negative relationship between income and flood damages. We examine the non-monotonic (inverted U-shaped) relationship between per capita income and flood impact in terms of deaths, people affected, and damages due to floods in 19 major Indian states from 1980 to 2011, using Poisson and Tobit estimation methods. In particular, deaths and the population affected by floods increase with a turning point of income up to 882 US$ and 578 US$, respectively, and diminishes thereafter. Our results confirm an inverted U-shaped relationship between income and fatalities and the population affected by floods. In addition to income, we argue that government responsiveness plays an essential role in mitigating the risk of floods. We employ the fixed-effect Poisson estimation method to examine the government's role in protecting people against disaster risk, focusing on regional differences in India. Deaths from floods remain non-linear and follow the inverted U-pattern with respect to government responsiveness. However, the effect of government responsiveness on flood fatalities and flood damages is statistically insignificant. Our results further suggest that high-income states experience a lower death toll from floods. The high-income (rich) states are capable of incurring a higher threshold level of income and higher natural calamity expenditure to reduce flood fatalities and protect the population affected by floods than the low-income (poor) states. The poor states have minimal resources and face severe financial constraints to reduce the death toll from floods. From the perspective of public policy, the poor states, in particular, require an increase in income, better governance, and effective disaster management policies to mitigate flood impact.
An anti-influenza combined therapy assessed by single cell RNA-sequencing
Authors: Medaglia Chiara , Kolpakov Ilya , Zwygart Arnaud Charles-Antoine , Zhu Yong , Constant Samuel , Huang Song , Cagno Valeria , Dermitzakis Emmanouil T. , Stellacci Francesco , Xenarios Ioannis , Tapparel Caroline
Published: October 2022

Influenza makes millions of people ill every year, placing a large burden on the healthcare system and the economy. To develop a treatment against influenza, we combined virucidal sialylated cyclodextrins with interferon lambda and demonstrated, in human airway epithelia, that the two compounds inhibit the replication of a clinical H1N1 strain more efficiently when administered together rather than alone. We investigated the mechanism of action of the combined treatment by single cell RNA-sequencing analysis and found that both the single and combined treatments impair viral replication to different extents across distinct epithelial cell types. We showed that each cell type comprises multiple sub-types, whose proportions are altered by H1N1 infection, and assessed the ability of the treatments to restore them. To the best of our knowledge this is the first study investigating the effectiveness of an antiviral therapy against influenza virus by single cell transcriptomic studies.
Benchmarking saliency methods for chest X-ray interpretation
Authors: Saporta Adriel , Gui Xiaotong , Agrawal Ashwin , Pareek Anuj , Truong Steven Q. H. , Nguyen Chanh D. T. , Ngo Van-Doan , Seekins Jayne , Blankenberg Francis G. , Ng Andrew Y. , Lungren Matthew P. , Rajpurkar Pranav
Published: October 2022

Saliency methods, which produce heat maps that highlight the areas of the medical image that influence model prediction, are often presented to clinicians as an aid in diagnostic decision-making. However, rigorous investigation of the accuracy and reliability of these strategies is necessary before they are integrated into the clinical setting. In this work, we quantitatively evaluate seven saliency methods, including Grad-CAM, across multiple neural network architectures using two evaluation metrics. We establish the first human benchmark for chest X-ray segmentation in a multilabel classification set-up, and examine under what clinical conditions saliency maps might be more prone to failure in localizing important pathologies compared with a human expert benchmark. We find that (1) while Grad-CAM generally localized pathologies better than the other evaluated saliency methods, all seven performed significantly worse compared with the human benchmark, (2) the gap in localization performance between Grad-CAM and the human benchmark was largest for pathologies that were smaller in size and had shapes that were more complex, and (3) model confidence was positively correlated with Grad-CAM localization performance. Our work demonstrates that several important limitations of saliency methods must be addressed before we can rely on them for deep learning explainability in medical imaging.
Rarest rainfall events will see the greatest relative increase in magnitude under future climate change
Authors: Gründemann Gaby Joanne , van de Giesen Nick , Brunner Lukas , van der Ent Ruud
Published: October 2022

Future rainfall extremes are projected to increase with global warming according to theory and climate models, but common (annual) and rare (decennial or centennial) extremes could be affected differently. Here, using 25 models from the Coupled Model Intercomparison Project Phase 6 driven by a range of plausible scenarios of future greenhouse gas emissions, we show that the rarer the event, the more likely it is to increase in a future climate. By the end of this century, daily land rainfall extremes could increase in magnitude between 10.5% and 28.2% for annual events, and between 13.5% and 38.3% for centennial events, for low and high emission scenarios respectively. The results are consistent across models though with regional variation, but the underlying mechanisms remain to be determined.
High-resolution phylogenetic and population genetic analysis of microbial communities with RoC-ITS
Authors: Rusch Douglas B , Huang Jie , Hemmerich Chris , Hahn Matthew W
Published: October 2022

Microbial communities are inter-connected systems of incredible complexity and dynamism that play crucial roles in health, energy, and the environment. To better understand microbial communities and how they respond to change, it is important to know which microbes are present and their relative abundances at the greatest taxonomic resolution possible. Here, we describe a novel protocol (RoC-ITS) that uses the single-molecule Nanopore sequencing platform to assay the composition of microbial communities at the subspecies designation. Using rolling-circle amplification, this methodology produces long-read sequences from a circular construct containing the complete 16S ribosomal gene and the neighboring internally transcribed spacer (ITS). These long reads can be used to generate a high-fidelity circular consensus sequence. Generally, the ribosomal 16S gene provides phylogenetic information down to the species-level, while the much less conserved ITS region contains strain-level information. When linked together, this combination of markers allows for the identification of individual ribosomal units within a specific organism and the assessment of their relative stoichiometry, as well as the ability to monitor subtle shifts in microbial community composition with a single generic assay. We applied RoC-ITS to an artificial microbial community that was also sequenced using the Illumina platform, to assess its accuracy in quantifying the relative abundance and identity of each species.