bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes and complications after open reduction and internal fixation of distal humeral fractures with precontoured locking plates
Authors: Rosenlund Anne-Mari N. , Søreide Endre , Madsen Jan Erik , Flugsrud Gunnar B. , Douglass Brenton W. , Midtgaard Kaare S. 
Published: October 2022

Abstract

Objectives:
The aim of this study was to evaluate functional and radiographic results after open reduction and internal fixation of distal humeral fractures using precontoured locking plates. Our main hypothesis was that patients older than 65 years have inferior outcomes compared with younger patients.

Methods:
All patients treated for a distal humeral fracture with precontoured locking plates between 2006 and 2017 at a level 1 trauma center were identified. Included patients underwent a clinical examination, and new radiographs were obtained. Functional outcomes were evaluated using Quick Disability of the Arm, Shoulder and Hand, Mayo Elbow Performance Score, visual analog scale elbow satisfaction, and range of motion. Complications and reoperations were recorded.

Results:
Fifty-seven patients with a median age of 60 years were included in this study. Median Quick Disability of the Arm, Shoulder and Hand was 14, and median Mayo Elbow Performance Score was 85. There was no difference in functional scores in patients younger than 65 years or 65 years or older. However, the median flexion–extension arc was 121 degrees in patients younger than 65 years and 111 degrees in patients 65 years or older (P = 0.01). The overall complication rate was 68%, and 24 patients had at least 1 reoperation. Ulnar neuropathy was the most common complication followed by reduced range of motion.

Conclusions:
Operative management of distal humeral fractures with precontoured locking plates provides good functional outcome. The patient-reported outcomes were good, independent of patient age. The implant failure rate is low with precontoured locking plates; however, the complication rate remains high, and reoperations are common.

Level of Evidence:
Level 4, retrospective study.
Clusters of facilitatory and inhibitory conditioned pain modulation responses in a large sample of children, adolescents, and young adults with chronic pain
Authors: Ocay Don Daniel , Ye Diana-Luk , Larche Cynthia L. , Potvin Stéphane , Marchand Serge , Ferland Catherine E. 
Published: October 2022

Abstract

Introduction:
When investigating the role of facilitatory and inhibitory pain mechanisms such as conditioned pain modulation (CPM) and temporal summation of pain (TSP), it is important to take both into consideration in a single experimental model to provide the most information on subgroups of patients. Therefore, the objective of this study was to identify subgroups in a large population of pediatric patients with chronic pain based on their facilitatory and inhibitory pain mechanisms and compare them with control subjects.

Methods:
Five hundred twenty-one female subjects and 147 male subjects between 8 and 21 years old underwent a CPM assessment using a 2-minute tonic noxious heat stimulation as the test stimulus and a 2-minute cold-pressor task (CPT) (12°C) as the conditioning stimulus.

Results:
The best partition of clusters of patients was 3 clusters accounting for 27.15% of the total variation in the data. Cluster 1 (n = 271) was best characterized by high pain intensity during the CPT, lack of TSP during the test stimuli, and efficient inhibitory CPM. Cluster 2 (n = 186) was best characterized by low pain intensity during the CPT, lack of TSP during the test stimuli, and efficient inhibitory CPM. Cluster 3 (n = 151) was best characterized by high pain intensity during the CPT, presence of TSP during the test stimuli, and inefficient inhibitory CPM.

Discussion:
A single thermal CPM experimental design can identify combinations of facilitatory and inhibitory pain modulation responses. Findings from the current study add to the literature by describing different clinical phenotypes of central pain mechanisms of youth with chronic pain.
Efficacy of Heart Rate Variability Biofeedback for Somatic Symptom Disorder: A Pilot Randomized Controlled Trial
Authors: Krempel Laura , Martin Alexandra 
Published: October 2022

ABSTRACT

Objective
Patients with somatic symptom disorder (SSD) often receive targeted intervention only after a long duration of illness. Moreover, the reported effect sizes of interventions for SSD are small. Therefore, improvement and evaluation of interventions are needed. Preliminary evidence suggests autonomic imbalance, for example, lower heart rate variability (HRV) in SSD. HRV biofeedback (HRV-BF) as a method for self-regulation shows initial positive effects in chronic pain and functional syndromes. The aim of this study was to evaluate the efficacy of a brief HRV-BF intervention for SSD.

Methods
Of a total of 50 participants with SSD (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) who were recruited and randomly assigned to four sessions of HRV-BF (n = 25) or autogenic training (AT; n = 25), 49 participants were analyzed (female, 77.6%; mean [standard deviation] age = 45.3 [14.4] years). The primary outcomes were somatic symptom severity (Screening for Somatoform Disorders, numeric rating scale) and HRV. Secondary outcomes were psychological characteristics of SSD (e.g., the Somatic Symptom Disorder 12 scale, health concerns, emotion regulation). The data were collected before and after intervention and were analyzed with repeated-measures analyses of variance and post hoc t tests.

Results
Symptom severity improved after both, HRV-BF and AT. Standard Deviation of the NN Interval and psychological symptoms improved significantly more strongly in the HRV-BF than in the AT group (e.g., Standard Deviation of the NN Interval: η
p
2 interaction = 0.10, p = .047).

Conclusions
The improvements in somatic symptoms, but specifically in cognitive-affective symptoms and autonomic regulation, suggest that HRV-BF with only four sessions is a potentially useful intervention option for SSD. Thus, adding this short HRV-BF intervention to existing psychological treatments for SSD may be promising.

Trial Registration: German Clinical Trial Register identifier DRKS00017099 (https://www.drks.de).
How to make calibration less painful – a proposition of an automatic, reliable and time-efficient procedure
Authors: Swider Karolina , Bruña Ricardo , Moratti Stephan 
Published: October 2022

AbstractBackgroundIn neurophysiological pain studies, multiple types of calibration methods are used to quantify the individual pain sensation stimuli that have different modalities. However, such studies often lack calibration procedure implementation, have a vague protocol description, do not provide data quality quantification, or even omit required control for gender pain differences. All this hampers not only study repetition but also interexperimental comparisons. Moreover, typical calibration procedures are long and require a high number of stimulations which may cause participants’ discomfort and stimuli habituation.MethodTo overcome those shortcomings, we present an automatic staircase pain calibration method for A-delta-specific electrical stimulation adjusted to the magnetoencephalography environment. We provide an in-depth data analysis of the collected self-reports from seventy healthy volunteers (37 males) and propose a method based on a dynamic truncated linear regression model (tLRM). We compare its estimates for the sensation (t), and pain (T) thresholds, as well as for the mid-pain stimulation (MP), with those calculated using a traditional threshold method and standard linear regression models.ResultsCompared to the other threshold methods, tLRM exhibits higher R2and requires 36% fewer stimuli application and has significantly highertand lowerTandMPintensities. Regarding sex differences, both lowertandTwere found for females compared to males, regardless of the calibration method.ConclusionsThe proposed tLRM method quantifies the quality of the calibration procedure, minimizes its duration and invasiveness, as well as provides validation of linearity between stimuli intensity and subjective scores, making it an enabling technique for further studies. Moreover, our results highlight the importance of control for gender in pain studies.SummaryThe purpose of this study was to shorten and automatize the calibration method which is an enabling technique for realizing neurophysiological studies on pain. The proposed method is based on a dynamic truncated linear regression model and was shown to require 36% fewer stimuli application compared to the traditional staircase method. Furthermore, the calibration was adjusted to A-delta specific intraepidermal electrical stimulation, quantifies the quality of the resulting calibration parameters and provides a validation of linearity between stimuli intensity and subjective scores. The results also highlight the importance of control for participant gender in studies where different types of stimulation are used to induce pain sensation.
Enhanced clinical assessment of hematologic malignancies through routine paired tumor:normal sequencing
Authors: Ptashkin Ryan N. , Ewalt Mark D. , Jayakumaran Gowtham , Kiecka Iwona , Bowman Anita S. , Yao JinJuan , Casanova Jacklyn , Lin Yun-Te David , Petrova-Drus Kseniya , Mohanty Abhinita S. , Bacares Ruben , Benhamida Jamal , Rana Satshil , Razumova Anna , Vanderbilt Chad , Remav Anoop Balakrishnan , Rijo Ivelise , Son-Garcia Julie , de Bruijn Ino , Zhu Menglei , Lachhander Sean , Wang Wei , Haque Mohammad S. , Seshan Venkatraman E. , Wang Jiajing , Liu Ying , Nafa Khedoudja , Borsu Laetitia , Zhang Yanming , Aypar Umut , Suehnholz Sarah P. , Chakravarty Debyani , Park Jae H. , Abdel-Wahab Omar , Mato Anthony R. , Xiao Wenbin , Roshal Mikhail , Yabe Mariko , Batlevi Connie Lee , Giralt Sergio , Salles Gilles , Rampal Raajit , Tallman Martin , Stein Eytan M. , Younes Anas , Levine Ross L. , Perales Miguel-Angel , van den Brink Marcel R. M. , Dogan Ahmet , Ladanyi Marc , Berger Michael F. , Brannon A. Rose , Benayed Ryma , Zehir Ahmet , Arcila Maria E. 
Published: October 2022

ABSTRACTGenomic profiling of hematologic malignancies has augmented our understanding of variants that contribute to disease pathogenesis and supported development of prognostic models that inform disease management in the clinic. Tumor only sequencing assays are limited in their ability to identify definitive somatic variants, which can lead to ambiguity in clinical reporting and patient management. Here, we describe the MSK-IMPACT Heme cohort, a comprehensive data set of somatic alterations from paired tumor and normal DNA using a hybridization capture-based next generation sequencing platform. We highlight patterns of mutations, copy number alterations, and mutation signatures in a broad set of myeloid and lymphoid neoplasms. We also demonstrate the power of appropriate matching to make definitive somatic calls, including in patients who have undergone allogeneic stem cell transplant. We expect that this resource will further spur research into the pathobiology and clinical utility of clinical sequencing for patients with hematologic neoplasms.
Enhanced mTORC1 signaling and Protein Synthesis in Parkinson’s Disease Pathogenesis Disease Pathogenesis
Authors: Khan Mohammed Repon , Yin Xiling , Kang Sung-Ung , Mitra Jaba , Wang Hu , Brahmachari Saurav , Karuppagounder Senthilkumar S. , Kimura Yasuyoshi , Jhaldiyal Aanishaa , Kim Hyun Hee , Gu Hao , Chen Rong , Redding-Ochoa Javier , Troncoso Juan , Ha Taekjip , Dawson Valina L. , Dawson Ted M. 
Published: October 2022

Pathologic α-syn destabilizes the TSC 1 and 2 complex leading to mTORC1 activation, enhanced protein translation and neurodegeneration in PD.Abstract:Pathological α-synuclein (α-syn) plays an important role in the pathogenesis of α-synucleinopathies such as Parkinson’s disease (PD). Disruption of protein homeostasis is thought be central to PD pathogenesis, however the molecular mechanism of this deregulation is poorly understood. Here we report that pathologic α-syn binds to tuberous sclerosis protein (TSC) 2 and destabilizes the TSC1-TSC2 complex leading to activation of the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and enhanced mRNA translation. Dopamine neuron loss, behavioral deficits and aberrant biochemical signaling in the α-syn preformed fibril (PFF) and Drosophila α-syn transgenic models of pathologic α-syn induced degeneration were attenuated by genetic and pharmacologic inhibition of mTOR and protein translation. Our findings establish a potential molecular mechanism by which pathologic α-syn activates mTORC1 leading to enhanced protein translation and concomitant neurodegeneration in PD.
Integration of silicon chip microstructures for in-line microbial cell lysis in soft microfluidics
Authors: Krishna Nittala Pavani Vamsi , Hohreiter Allison , Linhard Emilio Rosas , Dohn Ryan , Mishra Suryakant , Konda Abhiteja , Divan Ralu , Guha Supratik , Basu Anindita 
Published: October 2022

ABSTRACTThe paper presents fabrication methodologies that integrate silicon components into soft microfluidic devices to perform microbial cell lysis for biological applications. The integration methodology consists of a silicon chip that is fabricated with microstructure arrays and embedded in a microfluidic device, which is driven by piezoelectric actuation to perform cell lysis by physically breaking microbial cell walls via micromechanical impaction. We present different silicon microarray geometries, their fabrication techniques, integration of said microarrays into microfluidic devices, device operation and testing on synthetic microbeads and microbial cells to evaluate their efficacy. The generalized strategy developed for silicon chip integration into soft polymeric devices can serve as an important process step for a new class of hybrid silicon-polymeric devices for future cellular processing applications. The proposed integration methodology can be scalable and integrated as an in-line cell lysis tool with existing microfluidics assays.
The 5:2 diet does not increase adult hippocampal neurogenesis or enhance spatial memory in mice
Authors: Roberts Luke D. , Hornsby Amanda K. E. , Thomas Alanna , Sassi Martina , Kinzett Aimee , Hsiao Nathan , David Bethan R , Good Mark , Wells Timothy , Davies Jeffrey S. 
Published: October 2022

AbstractNew neurones are generated throughout life in the mammalian brain in a process known as adult hippocampal neurogenesis (AHN). Since this phenomenon grants a high degree of neuroplasticity influencing learning and memory and mood related behaviour, identifying factors that regulate AHN may be important for ameliorating age-related cognitive decline and neurodegeneration. Calorie restriction (CR), in the absence of malnutrition, has been shown to enhance AHN and improve hippocampal-dependent memory, mediated by the stomach hormone, ghrelin. Intermittent fasting (IF), a dietary strategy offering more flexibility than conventional CR, also promotes aspects of AHN. The 5:2 diet is a popular form of IF linked to a range of health benefits, however its effects on AHN and spatial memory are not well characterised. We hypothesised that the 5:2 diet would enhance AHN in a ghrelin-dependent manner.To assess this, we used immunohistochemistry to quantify new adult-born neurones and new neural stem cells (NSCs) in the hippocampal DG of adolescent and adult wild-type and mice lacking the ghrelin receptor following six weeks on a 5:2 diet. We report an age-related decline in neurogenic processes and identify a novel role for ghrelin-receptor in regulating the formation of new adult born NSCs in an age-dependent manner. However, the 5:2 diet did not affect new neurone or NSC formation in the DG. Consistent with this finding the 5:2 diet did not alter performance on a spatial learning and memory task. These data suggest that the 5:2 diet used in this study does not increase AHN or improve associated spatial memory function.Highlights5:2 diet does not increase adult hippocampal neurogenesis5:2 diet does not enhance spatial memory performanceThere is an age-related decline in adult hippocampal neurogenesisGhrelin-receptor regulates new neural stem cell and new neurone number in an age-related mannerGhrelin-receptor is required for intact spatial memory
Altered secretion, constitution, and functional properties of the gastrointestinal mucus in a rat model of sporadic Alzheimer’s disease
Authors: Homolak Jan , De Busscher Joke , Lucio Miguel Zambrano , Joja Mihovil , Virag Davor , Perhoc Ana Babic , Knezovic Ana , Barilar Jelena Osmanovic , Salkovic-Petrisic Melita 
Published: October 2022

AbstractAccumulating evidence supports the involvement of the gastrointestinal (GI) system in Alzheimer’s disease (AD), however, it is currently unknown whether GI alterations arise as a consequence of central nervous system (CNS) pathology or play a causal role in the pathogenesis of the disease. The GI mucus system is a possible mediator of GI dyshomeostasis in neurological disorders as CNS controls mucus production and secretion via the efferent arm of the brain-gut axis. The aim was to use a brain-first model of sporadic AD induced by intracerebroventricular streptozotocin (STZ-icv) to dissect the efferent (i.e. brain-to-gut) effects of isolated central neuropathology on the GI mucus system. Quantification and morphometric analysis of goblet cell mucigen granules revealed altered GI mucus secretion in the AD model possibly mediated by the insensitivity of AD goblet cells to neurally-evoked mucosal secretion confirmed by ex vivo cholinergic stimulation of isolated duodenal rings. The dysfunctional efferent control of the GI mucus secretion results in altered biochemical composition of the mucus associated with reduced glycoprotein aggregation and binding capacity in vitro. Finally, functional consequences of the reduced barrier-forming capacity of the AD mucus are demonstrated using the in vitro two-compartment caffeine diffusion interference model. Isolated central AD-like neuropathology results in the loss of efferent control of GI homeostasis via the brain-gut axis characterized by the insensitivity to neurally-evoked mucosal secretion, altered mucus constitution, and reduced barrier-forming capacity potentially increasing the susceptibility of STZ-icv rat model of AD to GI and systemic inflammation induced by intraluminal toxins, microorganisms, and drugs.
Entropic control of the free energy landscape of an archetypal biomolecular machine
Authors: Ray Korak Kumar , Kinz-Thompson Colin D. , Fei Jingyi , Wang Bin , Lin Qiao , Gonzalez Ruben L. 
Published: October 2022

ABSTRACTBiomolecular machines are complex macromolecular assemblies that utilize thermal and chemical energy to perform essential, multistep, cellular processes. Despite possessing different architectures and functions, an essential feature of the mechanisms-of-action of all such machines is that they require dynamic rearrangements of structural components. Surprisingly, biomolecular machines generally possess only a limited set of such motions, suggesting that these dynamics must be repurposed to drive different mechanistic steps. Although ligands that interact with these machines are known to drive such repurposing, the physical and structural mechanisms through which ligands achieve this remain unknown. Using temperature-dependent, single-molecule measurements analyzed with a time-resolution-enhancing algorithm, here we dissect the free energy landscape of an archetypal biomolecular machine, the bacterial ribosome, to reveal how its dynamics are repurposed to drive distinct steps during ribosome-catalyzed protein synthesis. Specifically, we show that the free energy landscape of the ribosome encompasses a network of allosterically coupled structural elements that coordinates the motions of these elements. Moreover, we reveal that ribosomal ligands which participate in disparate steps of the protein synthesis pathway repurpose this network by differentially modulating the structural flexibility of the ribosomal complex (i.e., the entropic component of the free energy landscape). We propose that such ligand-dependent entropic control of free energy landscapes has evolved as a general strategy through which ligands may regulate the functions of all biomolecular machines. Such entropic control is therefore an important driver in the evolution of naturally occurring biomolecular machines and a critical consideration for the design of synthetic molecular machines.
A graph-matching based metric of functional connectome distance between pairs of individuals varies with their ages, cognitive performances and familial relationships
Authors: Bukhari Hussain , Su Chang , Dhamala Elvisha , Gu Zijin , Jamison Keith , Kuceyeski Amy 
Published: October 2022

ABSTRACTFunctional connectomes (FCs), represented by networks or graphs that summarize coactivation patterns between pairs of brain regions, have been related at a population level to age, sex, cognitive/behavioral scores, life experience, genetics and disease/disorders. However, quantifying FC differences between pairs of individuals also provides a rich source of information with which to map to differences in those individuals’ biology, experience, genetics or behavior. In this study, graph matching is used to create a novel inter-individual FC metric, called swap distance, that quantifies the distance between pairs of individuals’ FCs. We apply graph matching to align FCs between pairs of individuals from the the Human Connectome Project (N = 997) and find that swap distance i) increases with increasing familial distance, ii) increases with subjects’ ages, iii) is smaller for pairs of females compared to pairs of males, and iv) is larger for females with lower cognitive scores compared to females with larger cognitive scores. Regions that contributed most to individuals’ swap distances were in higher-order networks, i.e. default-mode and fronto-parietal, that underlie executive function and memory. These higher-order networks’ regions also had swap frequencies that varied monotonically with familial relatedness of the individuals in question. We posit that the proposed graph matching technique provides a novel way to study inter-subject differences in FC and enables quantification of how FC may vary with age, relatedness, sex and behavior.
Competing neural representations of choice shape evidence accumulation in humans
Authors: Bond Krista , Rasero Javier , Madan Raghav , Bahuguna Jyotika , Rubin Jonathan , Verstynen Timothy 
Published: October 2022

Changing your mind requires shifting the way streams of information lead to a decision. Usingin silicoexperiments we show how the cortico-basal ganglia-thalamic (CBGT) circuits can feasibly implement shifts in the evidence accumulation process. When action contingencies change, dopaminergic plasticity redirects the balance of power, both within and between action representations, to divert the flow of evidence from one option to another. This finding predicts that when competition between action representations is highest, the rate of evidence accumulation is lowest. We then validate this prediction in a sample ofhomo sapiensas they perform an adaptive decision-making task while whole-brain hemodynamic responses are recorded. These results paint a holistic picture of how CBGT circuits manage and adapt the evidence accumulation process in mammals.One-sentence SummaryInteractions between cortical and subcortical circuits in the mammalian brain flexibly control the flow of information streams that drive decisions by shifting the balance of power both within and between action representations.