julilili42/papers huggingface dataset:
GestaltMatcher Database - A global reference for facial phenotypic variability in rare human diseases
2024-06-10

<title>Abstract</title> The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images – more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.
KCNQ1 is an essential mediator of the sex-dependent perception of moderate cold temperatures
2024-06-10

Low temperatures and cooling agents like menthol induce cold sensation by activating the peripheral cold receptors TRPM8 and TRPA1, cation channels belonging to the TRP channel family, while the reduction of potassium currents provides an additional and/or synergistic mechanism of cold sensation. Despite extensive studies over the past decades to identify the molecular receptors that mediate thermosensation, cold sensation is still not fully understood and many cold-sensitive peripheral neurons do not express the well-established cold sensor TRPM8. We found that the voltage-gated potassium channel KCNQ1 (Kv7.1), which is defective in cardiac LQT1 syndrome, is, in addition to its known function in the heart, a highly relevant and sex-specific sensor of moderately cold temperatures. We found that KCNQ1 is expressed in skin and dorsal root ganglion neurons, is sensitive to menthol and cooling agents, and is highly sensitive to moderately cold temperatures, in a temperature range at which TRPM8 is not thermosensitive. C-fiber recordings from KCNQ1 −/− mice displayed altered action potential firing properties. Strikingly, only male KCNQ1 −/− mice showed substantial deficits in cold avoidance at moderately cold temperatures, with a strength of the phenotype similar to that observed in TRPM8 −/− animals. While sex-dependent differences in thermal sensitivity have been well documented in humans and mice, KCNQ1 is the first gene reported to play a role in sex-specific temperature sensation. Moreover, we propose that KCNQ1, together with TRPM8, is a key instrumentalist that orchestrates the range and intensity of cold sensation.
IGF-1 and IGFBP-1 as Possible Predictors of Response to Lifestyle Intervention—Results from Randomized Controlled Trials
2024-06-10

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some individuals do not experience anticipated improvements despite weight loss. Biomarkers to identify such individuals at early stages are lacking. Insulin-like growth factor 1 (IGF- 1) and Insulin-like growth factor binding protein 1(IGFBP-1) were shown to predict T2DM onset in prediabetes. We assessed whether these markers also predict the success of lifestyle interventions, thereby possibly guiding personalized strategies. We analyzed the fasting serum levels of IGF-1, IGFBP-1, and Insulin-like growth factor binding protein 2 (IGFBP-2) in relation to changes in metabolic and anthropometric parameters, including intrahepatic lipids (IHLs) and visceral adipose tissue (VAT) volume, measured by magnetic resonance imaging (MRI), in 345 participants with a high risk for prediabetes (54% female; aged 36–80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), and significance was set at p &lt; 0.05. Within the 1-year intervention, overall significant improvements were observed. Stratifying individuals by baseline IGF-1 and IGFBP-1 percentiles revealed significant differences: higher IGF-1 levels were associated with more favorable changes compared to lower levels, especially in VAT and IHL. Lower baseline IGFBP-1 levels were associated with greater improvements, especially in IHL and 2 h glucose. Higher bioactive IGF-1 levels might predict better metabolic outcomes following lifestyle interventions in prediabetes, potentially serving as biomarkers for personalized interventions.
A Meta-Analysis on Teachers’ Growth Mindset
2024-06-10

The concept of growth mindset—an individual’s beliefs that basic characteristics such as intelligence are malleable—has gained immense popularity in research, the media, and educational practice. Even though it is assumed that teachers need a growth mindset and that both teachers and their students benefit when teachers adopt a growth mindset, systematic syntheses of the potential advantages of a growth mindset in teachers are lacking. Therefore, in this article, we present the first meta-analysis on teachers’ growth mindset and its relationships with multiple outcomes (50 studies, 81 effect sizes; N = 19,555). Multilevel analyses showed a small effect across outcomes. Statistically significant small-to-typical positive associations between teachers’ growth mindset and their motivation in terms of self-efficacy and mastery goals were observed in subgroup analyses. No statistically significant relationships were found with teachers’ performance-approach goals, teachers’ performance-avoidance goals, teachers’ performance on achievement tests, or student achievement. Teachers’ growth mindset was related to instructional practices in terms of mastery goal structures but unrelated to performance goal structures. Moderator analyses indicated that the dimensionality of the mindset measure (recoded from a fixed mindset to a growth mindset measure vs. assessed as a growth mindset), item referent and content of the mindset measure, publication status (published vs. unpublished), world region, educational level, and study quality influenced the strengths of some of the relationships. Overall, our findings extend knowledge about teachers’ mindset and add to the evidence base on teacher characteristics and their links to relevant outcomes.
Expanding the spectrum of phenotypes for MPDZ: Report of four unrelated families and review of the literature
2024-06-10

Abstract MPDZ , a gene with diverse functions mediating cell–cell junction interactions, receptor signaling, and binding multivalent scaffold proteins, is associated with a spectrum of clinically heterogeneous phenotypes with biallelic perturbation. Despite its clinical relevance, the mechanistic underpinnings of these variants remain elusive, underscoring the need for extensive case series and functional investigations. In this study, we conducted a systematic review of cases in the literature through two electronic databases following the PRISMA guidelines. We selected nine studies, including 18 patients, with homozygous or compound heterozygous variants in MPDZ and added five patients from four unrelated families with novel MPDZ variants. To evaluate the role of Mpdz on hearing, we analyzed available auditory electrophysiology data from a knockout murine model ( Mpdz em1(IMPC)J/em1(IMPC)J ) generated by the International Mouse Phenotyping Consortium. Using exome and genome sequencing, we identified three families with compound heterozygous variants, and one family with a homozygous frameshift variant. MPDZ ‐related disease is clinically heterogenous with hydrocephaly, vision impairment, hearing impairment and cardiovascular disease occurring most frequently. Additionally, we describe two unrelated patients with spasticity, expanding the phenotypic spectrum. Our murine analysis of the Mpdz em1(IMPC)J/em1(IMPC)J allele showed severe hearing impairment. Overall, we expand understanding of MPDZ ‐related phenotypes and highlight hearing impairment and spasticity among the heterogeneous phenotypes.
The hidden oases: unveiling trophic dynamics in Namib's fog plant ecosystem
2024-06-10

Abstract The Namib Desert is a hyperarid coastal desert where fog is a major moisture source. We hypothesized that the fog-harvesting grass Stipagrostis sabulicola establishes an important ecological niche, termed the "Fog-Plant-Oases" (FPOs), and serves as the primary carbon source for the invertebrate community. To determine this, we measured the natural variations of the stable carbon and nitrogen isotopes (δ 13 C and δ 15 N) of invertebrates as well as that of plant biomass and belowground detritus and estimated the contributions of the fog plants in their diets. Our findings revealed a complex trophic structure and demonstrated that S. sabulicola fuels carbon flow from lower to higher trophic levels in the aboveground food web. The distinct δ 13 C values of bacterial- and fungal-feeding nematodes indicated however the separation of the aboveground niche, which is primarily sustained by S. sabulicola , from the belowground niche, where wind-blown sediments may serve as the main energy source for the soil biota. Our findings further accentuate the critical role of S. sabulicola FPOs in establishing complex trophic dynamics and a distinctive food web within the hyperarid Namib dunes.
Perfusion in Pedicled skin flaps: Initial Insights from Smartphone-Based Thermal Imaging protocol
2024-06-10

Objective: The key to the success of pedicled skin flaps in the head and neck region is preserved perfusion. The use of thermal imaging can provide an indirect indicator of tissue perfusion, which consecutively would be of interest for perioperative prediction of the viability. The effectiveness of thermal imaging has already been demonstrated for assessing pedicled and free flaps [1]. This work investigates the implementation of SBTI as a noninvasive and cost-efficient method in clinical practice for predicting the vitality and perioperative monitoring of pedicled skin flaps in head and neck surgery. Methods: The FLIR One Pro camera was used for this pilot study (Teledyne FLIR LLC, Wilsonville, Oregon, United States). It is a multispectral camera that contains a near-infrared camera unit with a resolution of 160 x 120 pixels, a temperature range of 0 ° - 400 °C, and a thermal resolution of 70 millikelvin. For the study, after implementing the system, n = 11 skin flaps were photographed by SBTI (n=44) after marking (T1), after elevation (T2), after completed surgery (T3), and 24 hours postoperatively (T4), and the outcome was assessed clinically in correlation after one week by one surgeon. Results: The pedicled skin flaps examined all showed a preserved, uniform thermal image signature peri- and postoperatively for time points T1-4. This corresponded to a good postoperative result regarding the vitality of the tissue transfer in the clinical assessments 24 hours and one week postoperatively. Conclusion: The acquisition of a continuously obtained thermal image signature as a surrogate marker for preserved tissue perfusion by SBTI proved simple, inexpensive, noninvasive, and efficient in the present sentinel study. The application of SBTI has been primarily investigated in identifying perforators in large pedicled or free flaps. [2, 3] The concordance of the obtained thermal image signature with a positive clinical outcome suggests that the presented method is also suitable for perioperative prognostic statements on postoperative flap vitality in pedicled skin flaps and for monitoring those during surgery. Further studies are necessary for the implementation of this method in clinical practice to support the surgeon&amp;#039;s intraoperative decision-making in the future.
Selective knockdown of GABAA‐α2 subunit in the dorsal dentate gyrus in adulthood induces anxiety, learning and memory deficits and impairs synaptic plasticity
2024-06-10

Abstract Animal studies and clinical trials suggest that maintenance of gamma‐aminobutyric acid (GABA)‐ergic activity may be crucial in coping with stressful conditions, anxiety and mood disorders. Drugs highly efficient in promoting anxiolysis were shown to activate this system, particularly via the α2‐subunit of type A receptors (GABAA α2). Given the high expression of GABAA α2 in the dentate gyrus (DG) sub‐field of the hippocampus, we sought to examine whether manipulation of the α2 subunit in this area will evoke changes in emotional behaviour, memory and learning as well as in synaptic plasticity. We found that knockdown of GABAAα2 receptor specifically in the dorsal DG of rats caused increased anxiety without affecting locomotor activity. Spatial memory and learning in the Morris water maze were also impaired in GABAAα2 receptor knocked down rats, an effect accompanied by alterations in synaptic plasticity, as assessed by long‐term potentiation in the DG. Our findings provide further support to the notion that emotional information processing in the hippocampus may be controlled, at least in part, via the inhibitory GABAA α2 receptor subunit, opening a potential avenue for early interventions from pre‐ puberty into adulthood, as a strategy for controlling anxiety‐related psychopathology.
The Mixed‐Anion Compound La2S2(CN2)
2024-06-10

Abstract The new binary metal carbodiimide La 2 S 2 (CN 2 ) was synthesized via a solid‐state metathesis reaction. The crystal structure was solved and refined on the basis of single‐crystal X‐ray diffraction data with space group C 2/ m . The structure is represented by a layered arrangement, based on alternating layers of lanthanum, sulfide, and carbodiimide units. A close resemblance of the structure with that of La 2 O 2 C 2 is discussed, as well as the less‐common coordination number seven of the lanthanum atom.
Interpreting cooling dates and histories from laser ablation in-situ (U-Th-Sm)/He thermochronometry
2024-06-10

Abstract. Recent applications of the in-situ (U-Th-Sm)/He thermochronometry technique demonstrate its potential to address some of the analytical challenges associated with the whole-grain technique. In this study, we adapted state-of-the-art apatite and zircon production-ejection-diffusion models for application to in-situ dating methods, aiming to enhance the applicability of this technique to a broad range of geologic samples and applications. Our modifications to thermal history models include accommodation of the full range of stopping distances for alpha-particles and cylindrical grain geometries. This investigation focuses on several key aspects of in-situ data interpretation: (i) exploring the relationship between in-situ dates and the position of ablation spots across individual grains, (ii) assessing differences and similarities between whole-grain and in-situ dates, (iii) determining optimal strategies and performance for reconstructing cooling histories from in-situ (U-Th-Sm)/He data, and (iv) reporting the effects of radionuclide zoning on (U-Th-Sm)/He thermochronology. Results indicate that the measured in-situ helium distribution is a function of grain size, ablation spot position and size, and cooling history. Together, these analytical and natural factors result in systematic variations in in-situ dates with distance from the grain rim. Therefore, similar to whole-grain analyses, robust interpretation requires determining grain geometry and the distance of the laser spot to the nearest prismatic face. In most cases, resulting in-situ dates are approximately 30 % older than corresponding whole-grain dates, except for samples exhibiting negligible diffusional helium loss. Reconstruction of cooling histories using in-situ (U-Th-Sm)/He data can be achieved through single measurements in several grains with varying grain size and/or effective uranium content, or within a single grain with measurements taken at different distances from the grain rim. In addition, statistical analysis of a large compilation of measured radionuclide variations in apatite and zircon grains reveals that radionuclide zoning strongly impacts whole-grain analyses, but can be directly measured with the in-situ method. Overall, our results suggest that in-situ measurements for (U-Th-Sm)/He date determination offer a means to extract meaningful cooling signals from samples with poor reproducibility from traditional whole-grain techniques.
Reviewer #2 (Public Review): Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells
2024-06-10

Neuromodulators have major influences on the regulation of neural circuit activity across the nervous system. Nitric oxide (NO) has been shown to be a prominent neuromodulator in many circuits and has been extensively studied in the retina. Here, it has been associated with the regulation of light adaptation, gain control, and gap junctional coupling, but its effect on the retinal output, specifically on the different types of retinal ganglion cells (RGCs), is still poorly understood. In this study, we used two-photon Ca2+ imaging and multi-electrode array (MEA) recordings to measure light-evoked activity of RGCs in the ganglion cell layer in the ex vivo mouse retina. This approach allowed us to investigate the neuromodulatory effects of NO on a cell type-level. Our findings reveal that NO selectively modulates the suppression of temporal responses in a distinct subset of contrast-suppressed RGC types, increasing their activity without altering the spatial properties of their receptive fields. Given that NO release is triggered by quick changes in light levels under photopic conditions, we propose that these RGC types signal fast contrast changes to higher visual regions. Remarkably, we found that about one-third of the RGC types, recorded using two-photon Ca2+ imaging, exhibited consistent, cell type-specific adaptational response changes throughout an experiment, independent of NO. By employing a paired-recording paradigm, we could disentangle those additional adaptational response changes from drug-induced modulations. Taken together, our research highlights the selective neuromodulatory effects of NO on RGCs and emphasizes the need of considering non-pharmacological activity changes, like adaptation, in such study designs.
Author response: Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells
2024-06-10

Neuromodulators have major influences on the regulation of neural circuit activity across the nervous system.Nitric oxide (NO) has been shown to be a prominent neuromodulator in many circuits and has been extensively studied in the retina.Here, it has been associated with the regulation of light adaptation, gain control, and gap junctional coupling, but its effect on the retinal output, specifically on the different types of retinal ganglion cells (RGCs), is still poorly understood.In this study, we used two-photon Ca 2+ imaging and multi-electrode array (MEA) recordings to measure light-evoked activity of RGCs in the ganglion cell layer in the ex vivo mouse retina.This approach allowed us to investigate the neuromodulatory effects of NO on a cell type-level.Our findings reveal that NO selectively modulates the suppression of temporal responses in a distinct subset of contrast-suppressed RGC types, increasing their activity without altering the spatial properties of their receptive fields.Given that NO release is triggered by quick changes in light levels under photopic conditions, we propose that these RGC types signal fast contrast changes to higher visual regions.Remarkably, we found that about one-third of the RGC types, recorded using two-photon Ca 2+ imaging, exhibited consistent, cell type-specific adaptational response changes throughout an experiment, independent of NO.By employing a paired-recording paradigm, we could disentangle those additional adaptational response changes from drug-induced modulations.Taken together, our research highlights the selective neuromodulatory effects of NO on RGCs and emphasizes the need of considering non-pharmacological activity changes, like adaptation, in such study designs.
Reviewer #1 (Public Review): Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells
2024-06-10

Neuromodulators have major influences on the regulation of neural circuit activity across the nervous system. Nitric oxide (NO) has been shown to be a prominent neuromodulator in many circuits and has been extensively studied in the retina. Here, it has been associated with the regulation of light adaptation, gain control, and gap junctional coupling, but its effect on the retinal output, specifically on the different types of retinal ganglion cells (RGCs), is still poorly understood. In this study, we used two-photon Ca2+ imaging and multi-electrode array (MEA) recordings to measure light-evoked activity of RGCs in the ganglion cell layer in the ex vivo mouse retina. This approach allowed us to investigate the neuromodulatory effects of NO on a cell type-level. Our findings reveal that NO selectively modulates the suppression of temporal responses in a distinct subset of contrast-suppressed RGC types, increasing their activity without altering the spatial properties of their receptive fields. Given that NO release is triggered by quick changes in light levels under photopic conditions, we propose that these RGC types signal fast contrast changes to higher visual regions. Remarkably, we found that about one-third of the RGC types, recorded using two-photon Ca2+ imaging, exhibited consistent, cell type-specific adaptational response changes throughout an experiment, independent of NO. By employing a paired-recording paradigm, we could disentangle those additional adaptational response changes from drug-induced modulations. Taken together, our research highlights the selective neuromodulatory effects of NO on RGCs and emphasizes the need of considering non-pharmacological activity changes, like adaptation, in such study designs.