bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting Variation in Clinical Practice Patterns for Geriatric Trauma Care Using Social Network Analysis
Authors: Jarman Molly P. , Ruan Mengyuan , Tabata-Kelly Masami , Perry Brea L. , Lee Byungkyu , Boustani Malaz , Cooper Zara 
Published: June 2023

Objective:
To characterize hospital-level professional networks of physicians caring for older trauma patients as a function of trauma patient age distribution.

Summary Background Data:
The causal factors associated with between-hospital variation in geriatric trauma outcomes are poorly understood. Variation in physician practice patterns reflected by differences in professional networks might contribute to hospital-level differences in outcomes for older trauma patients.

Methods:
This is a population-based, cross-sectional study of injured older adults (age ≥65) and their physicians from January 1, 2014-December 31, 2015, using Healthcare Cost and Utilization Project inpatient data and Medicare claims from 158 hospitals in Florida. We used social network analyses to characterize hospitals in terms of network density, cohesion, small-worldness, and heterogeneity, then used bivariate statistics to assess the relationship between network characteristics and hospital-level proportion of trauma patients who were age ≥65.

Results:
We identified 107,713 older trauma patients and 169,282 patient-physician dyads. The hospital-level proportion of trauma patients who were age ≥65 ranged from 21.5% to 89.1%. Network density, cohesion, and small-worldness in physician networks were positively correlated with hospital geriatric trauma proportions (R=0.29, P<0.001; R =0.16, P=0.048; and R =0.19, P<0.001, respectively). Network heterogeneity was negatively correlated with geriatric trauma proportion (R=0.40, P<0.001).

Conclusions:
Characteristics of professional networks among physicians caring for injured older adults are associated with the hospital-level proportion of trauma patients who are older, indicating differences in practice patterns at hospitals with older trauma populations. Associations between inter-specialty collaboration and patient outcomes should be explored as an opportunity to improve treatment of injured older adults.
Does the Use of Probe-based Near-infrared Autofluorescence Parathyroid Detection Benefit Parathyroidectomy?
Authors: Kiernan Colleen M. , Thomas Giju , Patel Anuradha , Fan Run , Ye Fei , Willmon Parker A. , Solórzano Carmen C. 
Published: June 2023

Objective:
To evaluate the benefits of probe-based near-infrared autofluorescence (NIRAF) parathyroid identification during parathyroidectomy.

Background:
Intraoperative parathyroid gland identification during parathyroidectomy can be challenging, while additionally requiring costly frozen sections. Earlier studies have established NIRAF detection as a reliable intraoperative adjunct for parathyroid identification.

Methods:
Patients undergoing parathyroidectomy for primary hyperparathyroidism were prospectively enrolled by a senior surgeon (>20 years experience) and a junior surgeon (<5 years experience), while being randomly allocated to the probe-based NIRAF or control group. Data collected included procedure type, number of parathyroids identified with high confidence by the surgeon and the resident, number of frozen sections performed, parathyroidectomy duration, and number of patients with persistent disease at the first postoperative visit.

Results:
One hundred sixty patients were randomly enrolled under both surgeons to the probe group (n=80) versus control (n=80). In the probe group, parathyroid identification rate of the senior surgeon improved significantly from 3.2 to 3.6 parathyroids per patient (P<0.001), while that of the junior surgeon also rose significantly from 2.2 to 2.5 parathyroids per patient (P=0.001). Parathyroid identification was even more prominent for residents increasing significantly from 0.9 to 2.9 parathyroids per patient (P<0.001). Furthermore, there was a significant reduction in frozen sections utilized in the probe group versus control (17 vs 47, P=0.005).

Conclusion:
Probe-based NIRAF detection can be a valuable intraoperative adjunct and educational tool for improving confidence in parathyroid gland identification, while potentially reducing the number of frozen sections required.
Anamorelin in Japanese patients with cancer cachexia: an update
Authors: Wakabayashi Hidetaka , Arai Hidenori , Inui Akio 
Published: June 2023

Purpose of review
Anamorelin was approved for production and marketing in Japan on 22 January 2021 for cancer cachexia in non-small-cell lung cancer, gastric cancer, pancreatic cancer, and colorectal cancer. The authors describe the updates of anamorelin for cancer cachexia in Japan.

Recent findings
Recent evidence showed that anamorelin improved lean body mass, body weight, and appetite in patients with cancer cachexia in clinical practice. Anamorelin does not increase body weight in the severe-weight-loss group in cachectic patients with pancreatic cancer. Several case reports showed that anamorelin can cause cardiac adverse drug reactions. Among the cardiac adverse reactions, fatal arrhythmias should be monitored carefully even if it is the first dose. Anamorelin combined with nutrition, physical activity, and exercise may be more useful than anamorelin alone for treating cancer cachexia. An interim analysis from post-marketing all-case surveillance was performed; however, details have not yet been published. When anamorelin cannot be used for cancer cachexia, Kampo medicines can be considered as an option.

Summary
Anamorelin has changed the clinical practice of cancer cachexia in Japan. The authors hope that anamorelin is available for other disease-related cachexia along with appropriate multidisciplinary interventions.
Non-coding variants are a rare cause of recessive developmental disordersin transwith coding variants
Authors: Lord Jenny , Oquendo Carolina J , Martin-Geary Alexandra , Blakes Alexander JM , Arciero Elena , Domcke Silvia , Childs Anne-Marie , Low Karen , Rankin Julia ,   Genomics England Research Consortium, Baralle Diana , Martin Hilary C. , Whiffin Nicola 
Published: June 2023

AbstractPurposeIdentifying pathogenic non-coding variants in individuals with developmental disorders (DD) is challenging due to the large search space. It is common to find a single protein-altering variant in a recessive gene in DD patients, but the prevalence of pathogenic non-coding ;second hits;in transwith these is unknown.MethodsIn 4,073 genetically undiagnosed rare disease trio probands from the 100,000 Genomes project, we identified rare heterozygous loss-of-function (LoF) or ClinVar pathogenic variants in recessive DD-associated genes. Using stringent region-specific filtering, we identified rare non-coding variants on the other haplotype. Identified genes were clinically evaluated for phenotypic fit, and where possible, we performed functional testing using RNA-sequencing.ResultsWe found 2,430 probands with one or more rare heterozygous pLoF or ClinVar pathogenic variants in recessive DD-associated genes, for a total of 3,761 proband-variant pairs. For 1,366 (36.3%) of these pairs, we identified at least one rare non-coding variantin trans. After stringent bioinformatic filtering and clinical review, five were determined to be a good clinical fit (inALMS1, NPHP3, LAMA2, IGHMBP2andGAA).ConclusionWe developed a pipeline to systematically identify and annotate compound heterozygous coding/non-coding genotypes. Using this approach we uncovered new diagnoses and conclude that this mechanism is a rare cause of DDs.
The influence of movement speed on reward-based motor learning
Authors: van Mastrigt Nina M. , van der Kooij Katinka , Smeets Jeroen B. J. 
Published: June 2023

AbstractHuman movement is inevitably variable. This variability can be seen as a constraint to overcome, but it may also be a feature: being variable may result in the discovery of better movement solutions. Especially when feedback is limited to binary information on movement success or failure, variability is key for discovering which movements lead to success. Since moving faster increases variability, we aimed to answer the question whether movement speed can be harnessed to improve such reward-based motor learning. Subjects performed a stepping task in a slow and a fast session. They had to learn the gain between their step lengths and visual target distances on screen based on binary reward feedback. We successfully manipulated movement speed between sessions and participants could learn the gain in both sessions. We found no difference in learning between speed sessions, despite the fact that variability in gain increased in the fast relative to the slow session. To distinguish between different sources of variability, we estimated inevitable motor noise from the variability following successful trials. We estimated exploration as the additional variability following non-successful trials relative to following successful trials. We found no relation between variability sources and learning. In conclusion, reward-based motor learning is possible in a gain-learning task. In this task, moving faster did not lead to higher learning. Since the role of variability may differ between experimental tasks, whether movement speed can be harnessed to improve motor learning needs to be tested in other experimental tasks.
Genetic influences on motor learning and superperformance mutants revealed by random mutational survey of mouse locomotion
Authors: Jakkamsetti Vikram , Ma Qian , Angulo Gustavo , Scudder William , Beutler Bruce , Pascual Juan M. 
Published: June 2023

ABSTRACTEvolution depends upon genetic variations that influence physiology. As defined in a genetic screen, phenotypic performance may be enhanced or degraded by such mutations. We set out to detect mutations that influence motor function, including motor learning. Thus, we tested the motor effects of 36,444 non-synonymous coding/splicing mutations induced in the germline of C57BL/6J mice with N-ethyl-N-nitrosourea by measuring changes in the performance of repetitive rotarod trials while blinded to genotype. Automated meiotic mapping was used to implicate individual mutations in causation. 32,726 mice bearing all the variant alleles were screened. This was complemented with the simultaneous testing of 1,408 normal mice for reference. 16.3% of autosomal genes were thus rendered detectably hypomorphic or nullified by mutations in homozygosity and motor tested in at least 3 mice. This approach allowed us to identify superperformance mutations inRif1,Tk1,Fan1andMn1. These genes are primarily related, among other less well characterized functions, to nucleic acid biology. We also associated distinct motor learning patterns with groups of functionally related genes. These functional sets included preferentially histone H3 methyltransferase activity for mice that learnt at an accelerated rate relative to the rest of mutant mice. The results allow for an estimation of the fraction of mutations that can modify a behavior influential for evolution such as locomotion. They may also enable, once the loci are further validated and the mechanisms elucidated, the harnessing of the activity of the newly identified genes to enhance motor ability or to counterbalance disability or disease.
Discovery of New Broad-Spectrum Anti-Infectives for Eukaryotic Pathogens Using Bioorganometallic Chemistry
Authors: Lin Yan , Jung Hyeim , Bulman Christina A. , Ng James , Vinck Robin , O’Beirne Cillian , Moser Matthew S. , Tricoche Nancy , Peguero Ricardo , Li Robert W. , Urban Joseph F. , Pape Patrice Le , Pagniez Fabrice , Moretto Marco , Weil Tobias , Lustigman Sara , Cariou Kevin , Mitreva Makedonka , Sakanari Judy A. , Gasser Gilles 
Published: June 2023

ABSTRACTDrug resistance observed with many anti-infectives clearly highlights the need for new broad-spectrum agents to treat especially neglected tropical diseases (NTDs) caused by eukaryotic parasitic pathogens including fungal infections. Since these diseases target the most vulnerable communities who are disadvantaged by health and socio-economic factors, new agents should be, if possible, easy-to-prepare to allow for commercialization based on their low cost. In this study, we show that simple modification of one of the most well-known antifungal drugs, fluconazole, with organometallic moieties not only improves the activity of the parent drug but also broadens the scope of application of the new derivatives. These compounds were highly effectivein vivoagainst pathogenic fungal infections and potent against parasitic worms such asBrugia,which causes lymphatic filariasis andTrichuris,one of the soil-transmitted helminths that infects millions of people globally. Notably, the identified molecular targets indicate a mechanism of action that differs greatly from the parental antifungal drug, including targets involved in biosynthetic pathways that are absent in humans, offering great potential to expand our armamentarium against drug-resistant fungal infections and NTDs targeted for elimination by 2030. Overall, the discovery of these new compounds with broad-spectrum activity opens new avenues for the development of treatments for several current human infections, either caused by fungi or by parasites, including other NTDs, as well as newly emerging diseases.ONE-SENTENCE SUMMARYSimple derivatives of the well-known antifungal drug fluconazole were found to be highly effectivein vivoagainst fungal infections, and also potent against the parasitic nematodeBrugia,which causes lymphatic filariasis and againstTrichuris,one of the soil-transmitted helminths that infects millions of people globally.
Visual shape discrimination in goldfish, modelled with the neural circuitry of optic tectum and torus longitudinalis
Authors: Northmore David 
Published: June 2023

AbstractThe ability of fish to discriminate shapes visually is well documented. What is not understood are the neural mechanisms employed by fish and other vertebrates that lack a cerebral cortex to distinguish even simple geometric patterns. All the behavioral and anatomical data in fishes point to the midbrain optic tectum as the essential structure, but physiological studies of it have shown only circular contrast-detecting receptive fields and oriented edge detectors with nothing more elaborate that is reliable. Attempting to solve this conundrum, I built a model of tectum with neuron-like elements. When shown objects moving in space, the model forms an attentional locus that tracks one object on a retinotopic layer of simulated tectal pyramidal neurons. The object’s elementary features, when binned together, allow it to be distinguished from other objects to some extent; it fails when objects differ only in the features’ spatial relationships, which fish can use for discrimination. The model’s solution is to bias the attentional locus to the edges of a shape in imitation of goldfish that naturally attend to the top of shapes. Redirection of the attentional locus from a shape’s center is achieved by spatially offsetting synaptic inputs to the pyramidal neurons, effected by the torus longitudinalis (an elongated nucleus at the medial rim of each tectal lobe) and its prolific axonal projections to the pyramidal neurons. The model’s shape discrimination was compared to goldfish in the extensive behavioral data of Bowman & Sutherland (1969) who used shapes with points and projections. One test series showed that fish were sensitive to the relative number of points on the tops of shapes. In another, fish could be trained to discriminate points on the sides. By using different offset connections and only one elementary feature detector for small dark spots, the model successfully emulated the two sets of goldfish data, as judged by significant correlations between model response and fish discrimination over 21 pairs of shapes in each series.
Cell autonomous regulation of the activation of AgRP neurons by the melanocortin-3 receptor
Authors: Gui Yijun , Dahir Naima S. , Downing Griffin , Sweeney Patrick , Cone Roger D. 
Published: June 2023

SUMMARYThe melanocortin-3 receptor (MC3R) is a negative regulator of the central melanocortin circuitry via presynaptic expression on AgRP nerve terminals, from where it regulates GABA release onto secondary MC4R-expressing neurons. Hence, animals lacking MC3R (MC3R KO) exhibit hypersensitivity to MC4R agonists. However, MC3R KO mice also exhibit defective behavioral and neuroendocrine responses to fasting. Here, we demonstrate that MC3R KO mice exhibit defective activation of AgRP neurons in response to fasting and cold exposure, while exhibiting normal inhibition of AgRP neurons by sensory detection of food. Further, using an AgRP-specific MC3R knockout model, we show that the control of AgRP neuron activation by MC3R is cell-autonomous. One mechanism underlying this involves the response to ghrelin, which is also blunted in mice with AgRP-specific deletion of the MC3R. Thus, MC3R is a crucial player in the control of energy homeostasis by the central melanocortin system, not only acting presynaptically on AgRP neurons, but via AgRP cell-autonomous regulation of fasting- and cold-induced neuronal activation as well.
Natural dispersal is better than translocation for reducing risks of inbreeding depression in eastern black rhinoceros (Diceros bicornis michaeli)
Authors: Mellya Ronald V. K. , Hopcraft J. Grant C. , Mwakilema William , Eblate Ernest M. , Mduma Simon , Mnaya Bakari , Chuma Idrissa , Macha Emmanuel S. , Wambura Dickson , Fyumagwa Robert , Kilbride Elizabeth , Mable Barbara K. , Khan Anubhab 
Published: June 2023

AbstractDue to ever increasing anthropogenic impacts, many species survive only in small and isolated populations. Active conservation management to reduce extinction risk includes: increasing habitat connectivity; translocations from captive populations; or intense surveillance of highly protected closed populations. The fitness of individuals born under these scenarios may vary due to differences in selection pressures. However, the genetic impacts of such strategies are rarely assessed. Using whole genome sequences from cohorts of the critically endangered eastern black rhinoceros as a model, we compare the consequences of past conservation efforts. We find that offspring of individuals that had either dispersed from native populations (FROH>100Kb= 0.13) or translocated from captive populations (FROH>100Kb= 0.08) showed lower inbreeding compared to closed populations (FROH>100Kb= 0.17). However, the frequency of highly deleterious mutations was higher for offspring resulting from translocation compared to the other groups and this load was sheltered by higher heterozygosity. This could increase risks of inbreeding depression if captive founders subsequently inbreed after translocation. In contrast, native dispersers reduced the negative effects of inbreeding without compromising the benefits of past purging of deleterious mutations. Our study highlights the importance of natural dispersal and reiterates the importance of maintaining habitat corridors between populations.
Mutations in the Bone Morphogenetic Protein signaling pathway sensitize zebrafish and humans to ethanol-induced jaw malformations
Authors: Klem John R. , Schwantes-An Tae-Hwi , Abreu Marco , Suttie Michael , Gray Raeden , Vo Hieu , Conley Grace , Foroud Tatiana M. , Wetherill Leah ,   CIFASD, Lovely C. Ben 
Published: June 2023

AbstractFetal Alcohol Spectrum Disorders (FASD) describe ethanol-induced developmental defects including craniofacial malformations. While ethanol-sensitive genetic mutations contribute to facial malformations, the impacted cellular mechanisms remain unknown. Bmp signaling is a key regulator of epithelial morphogenesis driving facial development, providing a possible ethanol-sensitive mechanism. We found that zebrafish mutants for Bmp signaling components are ethanol-sensitive and affect anterior pharyngeal endoderm shape and gene expression, indicating ethanol-induced malformations of the anterior pharyngeal endoderm cause facial malformations. Integrating FASD patient data, we provide the first evidence that variants in the human Bmp receptor geneBMPR1Bassociate with ethanol-related differences in jaw volume. Our results show that ethanol exposure disrupts proper morphogenesis of, and tissue interactions between, facial epithelia that mirror overall viscerocranial shape changes and are predictive for Bmp-ethanol associations in human jaw development. Our data provide a mechanistic paradigm linking ethanol to disrupted epithelial cell behaviors that underlie facial defects in FASD.Summary StatementIn this study, we apply a unique combination of zebrafish-based approaches and human genetic and facial dysmorphology analyses to resolve the cellular mechanisms driven by the ethanol-sensitive Bmp pathway.
Identification of spatial homogeneous regions in tissues with concordex
Authors: Jackson Kayla C. , Booeshaghi A. Sina , Gálvez-Merchán Ángel , Moses Lambda , Chari Tara , Kim Alexandra , Pachter Lior 
Published: June 2023

AbstractSpatial homogeneous regions (SHRs) in tissues are domains that are homogeneous with respect to cell type composition. We present a method for identifying SHRs using spatial transcriptomics data, and demonstrate that it is efficient and effective at finding SHRs for a wide variety of tissue types. The method is implemented in a tool called concordex, which relies on analysis of k-nearest-neighbor (kNN) graphs. The concordex tool is also useful for analysis of non-spatial transcriptomics data, and can elucidate the extent of concordance between partitions of cells derived from clustering algorithms, and transcriptomic similarity as represented in kNN graphs.