bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonoperative Versus Operative Treatment of Type IIA Supracondylar Humerus Fractures: A Prospective Evaluation of 99 Patients
Authors: Sanders Julia S. , Ouillette Ryan J. , Howard Roland , Boutelle Kelly , Carroll Alyssa N. , Bastrom Tracey P. , Paik Christina , Stearns Philip , Pennock Andrew T. , Upasani Vidyadhar V.
Published: December 2022

Background:

Although current clinical practice guidelines from the American Academy of Orthopaedic Surgeons suggest that Type II and III supracondylar humerus (SCH) fractures be treated by closed reduction and pin fixation, controversy remains as to whether type IIa fractures with no rotation or angular deformity require surgery. The purpose of our study was to prospectively compare radiographic and functional outcomes of type IIa SCH fractures treated with or without surgery.

Methods:

Between 2017 and 2019, 105 patients between 2 and 12 years of age presenting with type IIa SCH fractures and without prior elbow trauma, neuromuscular or metabolic conditions, were prospectively enrolled. Ten orthopaedic surgeons managed the patients with 5 preferring surgical treatment and 5 preferring an initial attempt at nonoperative treatment. Patients in the nonoperative cohort were managed with a long-arm cast and close radiographic follow-up. Patients underwent a standardized protocol, including 3 to 4 weeks of casting, bilateral radiographic follow-up 6 months postinjury, and telephone follow-up at 6, 12, and 24 months.

Results:

Ninety-nine patients met the inclusion criteria (45 nonoperative and 54 operatives). Of the nonoperative patients, 4 (9%) were converted to surgery up to their first clinical follow-up. No differences were identified between the cohorts with respect to demographic data, but patients undergoing surgery had on average 6 degrees more posterior angulation at the fracture site preoperatively (P<0.05). At the final clinical follow-up (mean=6 mo), the nonoperative group had more radiographic extension (176.9 vs 174.4 degrees, P=0.04) as measured by the hourglass angle, but no other clinical or radiographic differences were appreciated. Complications were similar between the nonoperative and operative groups: refracture (4.4 vs 5.6%), avascular necrosis (2.2 vs 1.9%) and infection (0 vs 1.9%) (P>0.05). Patient-reported outcomes at a mean of 24 months showed no differences between groups.

Conclusion:

Contrary to American Academy of Orthopaedic Surgeons guidelines, about 90% of patients with type IIa supracondylar fractures can be treated nonoperatively and will achieve good radiographic and functional outcomes with mild residual deformity improving over time. Patients treated nonoperatively must be monitored closely to assess for early loss of reduction and the need for surgical intervention.
Supracondylar Dome Osteotomy With a Posterior Triceps-splitting Approach for Acute Correction of Posttraumatic Cubital Axis Deformities in Adolescent Patients
Authors: Herzog Alexander N. , Wirth Thomas , Fernandez Francisco F.
Published: December 2022

Background:

Fractures around the elbow are common in children. Their management remains challenging. Inadequate treatment often leads to malunion, causing growth disturbance or avascular necrosis. This can develop into cubital axis deformities. This study evaluated our modified supracondylar dome osteotomy technique for acute correction of posttraumatic cubital axis deformities in adolescent patients.

Methods:

Eighteen cases of posttraumatic cubital axis deformity that underwent acute correction through supracondylar dome osteotomy in our department between 2012 and 2019 were retrospectively evaluated. The radiologic results were measured through the carrying angle. The clinical functional outcomes were assessed using the Mayo Elbow Performance Index.

Results:

No neurovascular injuries occurred and there was no notable loss of muscular strength or functional deficiencies in any of the patients. Symmetrical cubital axes were achieved in all cases. All cases were consolidated in a timely matter and no malunion was observed upon consolidation. Besides 1 case of hardware damage caused by a severe fall due to heavy alcohol intoxication, there was no correction loss, no secondary displacement, and no implant-related discomfort. None of the patients were left with a limited range of motion or reduced weight-bearing capacity. An excellent level of elbow functionality was achieved in all cases, with an average Mayo Elbow Performance Index of 97.8.

Conclusions:

The supracondylar dome osteotomy technique showed promising results in both radiologic outcomes and clinical performance, with a low complication rate. The dome-shaped osteotomy allows simultaneous multiplanar correction of not only varus or valgus deformities but also additional extension or flexion deformities. This technique also enables translation of the distal fragment in the frontal plane, which contributes to a more balanced anatomic geometry of the distal humerus. We consider the posterior triceps-splitting approach to be a safe technique that preserves muscle strength and improves the cosmetic appearance of the surgical scar. We recommend a cast-free plate fixation to allow early movement after surgery. We believe any residual deformities that present 18 months after the initial trauma should be addressed through surgical correction before clinical symptoms become apparent to avoid the chronic manifestation of functional deficiencies.

Level of Evidence:

Level IV, therapeutic study, case series.
Iliac Crest Bone Graft With Intramedullary Headless Implant for Metacarpal Bone Loss
Authors: Milhoan Madison , Hoelscher Victoria , Pientka William F.
Published: December 2022

Metacarpal bone loss presents a challenging reconstructive dilemma for hand surgeons. While multiple bone grafting techniques have been described, complications including nonunion, graft resorption, fixation requiring prolonged immobilization, stiffness, and the need for multiple procedures are well-documented. We present a technique for managing metacarpal bone loss utilizing a tri-cortical iliac crest graft and an intramedullary metacarpal nail for the treatment of metacarpal fractures and nonunions that is technically simple, fast, and allows for early initiation of motion to decrease postoperative complications.

Level of Evidence:

Level IV- Therapeutic
Postpartum medical management of hypertension and risk of readmission for hypertensive complications
Authors: Lovgren Todd , Connealy Brendan , Yao Ruofan , D. Dahlke Joshua
Published: December 2022

Objective:

To compare the risk of readmission in those receiving no treatment, labetalol, nifedipine or both at hospital discharge following delivery complicated by presence of hypertension.

Study design:

Retrospective study at a single tertiary care center over a 4-year period (2017–2020). Those with peripartum hypertension (pHTN), defined as any SBP greater than 140 mmHg or DBP greater than 90 mmHg on two occasions 4 h apart during their admission for delivery were included. The primary outcome was postpartum readmission because of hypertensive complications. Analysis was stratified by medication prescribed at discharge (no treatment prescribed, labetalol, nifedipine, or both). The risks of readmission for the management of pHTN were estimated using logistic regression and adjusted for confounding variables.

Results:

Nineteen thousand, four hundred and twenty-five women gave birth during the study period and 4660 (24.0%) met the described definition of pHTN. Of those, 1232 (26.4%) were discharged on antihypertensive medication (s). There were 217 (4.7%) readmissions for hypertensive complications following discharge. Compared with patients who did not receive antihypertensive medication at discharge, any nifedipine prescription was found to significantly decrease the risk of readmission: monotherapy [aOR 0.27 (0.15–0.48)], nifedipine with labetalol [aOR 0.35 (0.16–0.77)]. Labetalol monotherapy was associated with increased risk of readmission [aOR 1.66 (1.06–2.61)].

Conclusion:

The risk of postpartum readmission for hypertensive complication was reduced by 65% when patients were discharged on nifedipine monotherapy and 56% with combined nifedipine and labetalol treatment when compared with no treatment. Patients discharged on labetalol monotherapy were nearly six times as likely to be readmitted for hypertensive complications when compared with patients on nifedipine monotherapy.
Knowledge and Attitude About Pre-exposure Prophylaxis Among Primary Care Clinicians at a Federally Qualified Health Center in Central Texas: A Cross-sectional Study
Authors: Norwood Aliza , Zuñiga Julie A.
Published: December 2022

Pre-exposure prophylaxis (PrEP) for HIV prevention is a highly effective tool in preventing HIV, yet PrEP is underprescribed. Primary care providers are ideally positioned to increase access to and awareness of PrEP, but health care providers' knowledge of PrEP greatly varies. To evaluate PrEP knowledge and attitudes of primary care providers, we conducted a descriptive cross-sectional study examining primary providers' knowledge and concerns about PrEP. Participants (n = 122) included physicians, nurses, pharmacists, and residency trainees in family medicine, internal medicine, and obstetrics. Despite high awareness of PrEP among these primary care providers (91.7%), fewer reported feeling comfortable prescribing PrEP (62.5%), and the average number of PrEP prescriptions per provider written in the last 6 months was less than 1. PrEP remains key to preventing HIV, but prescriptions remain low. Health care providers would benefit from additional education and training on communicating with their patients about sexual health and HIV prevention.
Barriers and facilitators to nurse practitioner buprenorphine prescribing for opioid use disorder in primary care settings
Authors: Speight Chandra , Caiola Courtney , Tyndall Deborah E. , Scott Elaine S.
Published: December 2022

Background:

Increasing access to opioid use disorder (OUD) treatment is critical to curbing the opioid epidemic, particularly for rural residents who experience numerous health and health care disparities, including higher overdose death rates and limited OUD treatment access compared with urban dwellers. Buprenorphine–naloxone is an evidence-based treatment for OUD that is well suited for rural areas. However, providers must have a specialized federal waiver to prescribe the medication. Despite the acceleration of the opioid epidemic in rural areas and the recent liberalization of federal buprenorphine–naloxone prescribing laws, few providers hold buprenorphine–naloxone prescribing waivers and even fewer prescribe the medication.

Purpose:

This study explores barriers and facilitators to buprenorphine–naloxone prescribing among nurse practitioners (NPs) working in primary care settings in eastern North Carolina.

Methodology:

Individual interviews were conducted with 13 NPs working in primary care settings in eastern North Carolina. Qualitative thematic analysis was used to identify perceived barriers and facilitators to buprenorphine–naloxone prescribing.

Results:

Analysis found prescribing barriers related to OUD stigma, perceived knowledge, federal and state regulation, and prescribing resources and found facilitators related to adopting a person-centered approach, developing prescriber skills, and access to prescribing resources.

Conclusions:

The barriers and facilitators that NPs experience related to buprenorphine prescribing for OUD are similar to those faced by physicians, although the barriers arguably more profound. Future research should consider how to mitigate these prescribing barriers to facilitate NP buprenorphine prescribing for OUD.

Implications:

To our knowledge, this is the first qualitative study of NP buprenorphine–naloxone prescribing in rural areas. Given the prominence of OUD in rural regions and the key role NPs play in primary care provision, this study lays import groundwork for developing interventions to support buprenorphine–naloxone prescribing by NPs practicing in rural regions.
Significance of Baseline Inferior Vestibular Function on the Prognosis of Patients with Labyrinthitis
Authors: Cho Ji-Woong , Cho Sung Il , Baek Wonyong , Kim Min Seok , Nam Gi-Sung
Published: December 2022

Objective

Acute spontaneous vertigo with idiopathic sudden sensorineural hearing loss (ISSNHL) can be diagnosed as labyrinthitis, which has a poorer prognosis than ISSNHL without vertigo. Thus, we aimed to identify the effect of the baseline vestibular function on the prognosis of labyrinthitis.

Methods

A total of 23 patients with labyrinthitis was retrospectively divided into the recovered group (complete recovery, partial recovery) and the nonrecovered group (slight improvement, no improvement). Differences in caloric weakness and gain in the video head impulse test (vHIT) between the two groups were compared. In addition, the prognostic value of the vHIT on each of the three semicircular canals in predicting hearing recovery was analyzed using a linear regression model.

Results

In final pure-tone audiometry, 2 patients (8.70%) exhibited complete recovery, 4 patients (17.39%) had partial recovery, and 17 patients (73.91%) had slight or no improvement. The initial ipsilesional posterior canal (iPC) gain and the contralesional anterior canal (cAC) gain were significantly decreased in the nonrecovered group (p < 0.013 for iPC and p < 0.007 for cAC, Mann–Whitney U test). The mean hearing gain was positively correlated with the iPC gain (R
2 = 0.36, p = 0.003, Spearman correlation analysis).

Conclusion

An abnormal iPC gain may be a poor prognostic factor for hearing recovery. Additionally, the vHIT on the three semicircular canals can provide prognosis and insights into the pathophysiological mechanisms in patients with labyrinthitis.
Classifying the Large Vestibular Aqueduct: Morphometry to Audiometry
Authors: Deep Nicholas L. , Carlson Matthew L. , Hoxworth Joseph M. , Driscoll Colin L. W. , Lohse Christine M. , Lane John I. , Ho Mai-Lan
Published: December 2022

Objective

Large vestibular aqueduct (LVA) is the most common inner ear dysplasia identified in patients with hearing loss. Our objective was to systematically quantify LVA morphologies and correlate imaging findings with established audiometric outcomes.

Study Design

Retrospective review.

Setting

Tertiary referral center.

Patients

Patients with large vestibular aqueduct identified radiographically, with or without hearing loss.

Intervention(s)

Diagnostic only.

Main Outcome Measure(s)

Vestibular aqueduct (VA) width at midpoint, width at external aperture, and length were measured on cross-sectional imaging. Morphology was classified as type I (borderline), type II (tubular), or type III (funneled). Audiometric endpoints included air/bone conduction, pure tone averages, and air-bone gaps at 250 and 500 Hz. Statistical associations were evaluated using linear regression models, adjusted for age at first audiogram and sex.

Results

One hundred seventeen patients (197 ears) were included, with mean age at first audiogram of 22.2 years (standard deviation, 21.7 yr). Imaging features associated with poor audiometric outcomes were increasing VA width at midpoint and external aperture, decreasing VA length, dilated extraosseous endolymphatic sac, cochleovestibular malformations, and increasing VA type (III > II > I).

Conclusions

Quantitative LVA measurements and a standardized morphologic classification system aid in prediction of early audiometric endpoints.
Measuring the Angular Accuracy of a Clinician-Performed Epley Maneuver Used to Treat Benign Paroxysmal Positional Vertigo
Authors: Murphy Claudine , Keogh Ivan J.
Published: December 2022

Introduction

Particle repositioning maneuvers have become the criterion standard for managing benign paroxysmal positional vertigo. The Epley canalolith repositioning maneuver is used to treat posterior canal benign paroxysmal positional vertigo and is successful in up to 90% of cases. However, when performed, there are many clinician variabilities, and angles are approximate. It is not known how accurate each angle needs to be for the target canal to be adequately stimulated. The objective of this study was to measure the angular accuracy of clinician-guided Epley maneuvers using a three-axis accelerometer.

Methods

Ten healthy subjects were recruited; participants had no known audio vestibular pathology. Five right-hand–dominant clinicians performed Epley maneuvers on both ears of two different participants. Twenty maneuvers were carried out in total. Angular movements were recorded using a vestibular feedback electronic device, the SHIMMER accelerometer. Data were recorded and analyzed using the EYESWEB Open Platform.

Results

Results showed that there was angular error at every stage of the clinician-performed Epley maneuver. The most accurate movement was positioning the head to the left of 45 degrees for a left ear maneuver with an average error of 2.94 degrees. The least accurate was when positioning the patient to face the floor at 135 degrees from supine for a right ear maneuver with an average error of 17.6 degrees.

Conclusion

Even when experienced ENT clinicians perform a standard Epley maneuver, there is a wide range of angular inaccuracy at each stage. Face to floor is particularly inaccurate. However, given that a majority of procedures (90%) work on the first attempt, there must be an acceptable but unknown range of angular inaccuracy. Novel technologies could improve the angular accuracy, potentially give better results, and allow a broad range of individuals to perform a more accurate Epley maneuver.
Subtemporalis Muscle Middle Cranial Fossa Bone-Island Craniotomy Technique for Placement of an Active Transcutaneous Bone-Conduction Implant
Authors: Shapiro Scott B. , Llerena Pablo A. , Mowery Todd M. , Miele Erica A. , Wackym P. Ashley
Published: December 2022

Objective

Placement of an active transcutaneous bone-conduction implant (BCI) requires drilling of a precise bone bed to accommodate the device and allow for fixation points to make appropriate contact with bone, which can be difficult even when lifts are used. We describe a subtemporalis muscle middle cranial fossa bone-island craniotomy technique that simplifies the procedure and obviates the need for lifts in securing the device.

Study Design

Prospective case series.

Setting

Tertiary academic medical center.

Patients

Seventeen patients underwent surgery for placement of 18 transcutaneous BCIs, 14 for conductive or mixed hearing loss, and 4 for single-sided deafness.

Interventions

Surgical placement of a transcutaneous BCI with a bone-island craniotomy technique.

Main Outcome Measures

Functional gain in air-conduction thresholds, aided air-bone gap, frequency of need for lifts, and minor and major complications.

Results

For the conductive or mixed hearing loss cohort, with the transcutaneous BCI in place, there was a highly statistically significant mean functional gain of 35.4 dB hearing level (HL) (range, 16.7–50.25 dB HL; standard deviation, 12.4 dB HL) compared with the unaided condition (p < 0.0001; 95% confidence interval, 36.6–51.6 dB HL). Lifts were not needed in any case. There was one minor complication requiring a second procedure in a patient who had previously received radiation and no major complications. There was no device loss or failure.

Conclusions

A subtemporalis muscle middle cranial fossa bone-island craniotomy technique eliminates the need for lifts and is a safe and effective method for placement of a transcutaneous BCI.
Cardiometabolic syndrome in HIV-positive and HIV-negative patients at Zewditu Memorial Hospital, Addis Ababa, Ethiopia: a comparative cohort study
Authors: Woldu Minyahil , Minzi Omary , Shibeshi Workineh , Shewaamare Aster , Engidawork Ephrem
Published: December 2022

Background

Cardiometabolic syndrome (CMetS) has recently emerged as a serious public health concern, particularly for individuals living with chronic conditions. This study aimed to determine the incidence and prevalence of CMetS, as well as the risk factors linked with it, in HIV-positive and HIV-negative adult patients.

Methods

A comparative cohort study was designed. The National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) tools were used to determine the outcome variables. Association studies were done using logistic regression.

Result

CMetS was found to have a greater point and period prevalence, and incidence estimation in HIV-negative than HIV+ patients using both the NCEP and the IDF tools. Using the NCEP tool, the risk of obesity was 44.1% [odds ratio (OR) = 0.559, 95% confidence interval (CI), (0.380–0.824); P = 0.003] lower in HIV+ than in HIV-negative participants. By contrast, no apparent difference was noted using the IDF tool. Similarly, hyperglycemia [OR = 0.651, 95% CI (0.457–0.926); P = 0.017], and hypertension [OR = 0.391, 95% CI (0.271–0.563); P < 0.001] were shown to be lower in HIV+ patients than HIV-negative patients by 34.9% and 60.9%, respectively. The study revealed significant variation in all biomarkers across the follow-up period in both HIV+ and HIV-negative participants, except for SBP.

Conclusions

CMetS caused more overall disruption in HIV-negative people with chronic diseases than in HIV-positive people. All of the indicators used to assess the increased risk of CMetS were equally meaningful in HIV+ and HIV-negative subjects.
Understanding 3D vision as a policy network
Authors: Glennerster Andrew
Published: December 2022

It is often assumed that the brain builds 3D coordinate frames, in retinal coordinates (with binocular disparity giving the third dimension), head-centred, body-centred and world-centred coordinates. This paper questions that assumption and begins to sketch an alternative based on, essentially, a set of reflexes. A ‘policy network’ is a term used in reinforcement learning to describe the set of actions that are generated by an agent depending on its current state. This is an untypical starting point for describing 3D vision, but a policy network can serve as a useful representation both for the 3D layout of a scene and the location of the observer within it. It avoids 3D reconstruction of the type used in computer vision but is similar to recent representations for navigation generated through reinforcement learning. A policy network for saccades (pure rotations of the camera/eye) is a logical starting point for understanding (i) an ego-centric representation of space (e.g. Marr’s (Marr 1982
Vision: a computational investigation into the human representation and processing of visual information
) 2

1
2

-D sketch) and (ii) a hierarchical, compositional representation for navigation. The potential neural implementation of policy networks is straightforward; a network with a large range of sensory and task-related inputs such as the cerebellum would be capable of implementing this input/output function. This is not the case for 3D coordinate transformations in the brain: no neurally implementable proposals have yet been put forward that could carry out a transformation of a visual scene from retinal to world-based coordinates. Hence, if the representation underlying 3D vision can be described as a policy network (in which the actions are either saccades or head translations), this would be a significant step towards a neurally plausible model of 3D vision.

This article is part of the theme issue ‘New approaches to 3D vision’.
Walking humans and running mice: perception and neural encoding of optic flow during self-motion
Authors: Horrocks Edward A. B. , Mareschal Isabelle , Saleem Aman B.
Published: December 2022

Locomotion produces full-field optic flow that often dominates the visual motion inputs to an observer. The perception of optic flow is in turn important for animals to guide their heading and interact with moving objects. Understanding how locomotion influences optic flow processing and perception is therefore essential to understand how animals successfully interact with their environment. Here, we review research investigating how perception and neural encoding of optic flow are altered during self-motion, focusing on locomotion. Self-motion has been found to influence estimation and sensitivity for optic flow speed and direction. Nonvisual self-motion signals also increase compensation for self-driven optic flow when parsing the visual motion of moving objects. The integration of visual and nonvisual self-motion signals largely follows principles of Bayesian inference and can improve the precision and accuracy of self-motion perception. The calibration of visual and nonvisual self-motion signals is dynamic, reflecting the changing visuomotor contingencies across different environmental contexts. Throughout this review, we consider experimental research using humans, non-human primates and mice. We highlight experimental challenges and opportunities afforded by each of these species and draw parallels between experimental findings. These findings reveal a profound influence of locomotion on optic flow processing and perception across species.

This article is part of a discussion meeting issue ‘New approaches to 3D vision’.
Do you hear what I see? How do early blind individuals experience object motion?
Authors: Fine Ione , Park Woon Ju
Published: December 2022

One of the most important tasks for 3D vision is tracking the movement of objects in space. The ability of early blind individuals to understand motion in the environment from noisy and unreliable auditory information is an impressive example of cortical adaptation that is only just beginning to be understood. Here, we compare visual and auditory motion processing, and discuss the effect of early blindness on the perception of auditory motion. Blindness leads to cross-modal recruitment of the visual motion area hMT+ for auditory motion processing. Meanwhile, the planum temporale, associated with auditory motion in sighted individuals, shows reduced selectivity for auditory motion. We discuss how this dramatic shift in the cortical basis of motion processing might influence the perceptual experience of motion in early blind individuals.

This article is part of a discussion meeting issue ‘New approaches to 3D vision’.
The role of binocular vision in the control and development of visually guided upper limb movements
Authors: Niechwiej-Szwedo Ewa , Colpa Linda , Wong Agnes
Published: December 2022

Vision provides a key sensory input for the performance of fine motor skills, which are fundamentally important to daily life activities, as well as skilled occupational and recreational performance. Binocular visual function is a crucial aspect of vision that requires the ability to combine inputs from both eyes into a unified percept. Summation and fusion are two aspects of binocular processing associated with performance advantages, including more efficient visuomotor control of upper limb movements. This paper uses the multiple processes model of limb control to explore how binocular viewing could facilitate the planning and execution of prehension movements in adults and typically developing children. Insight into the contribution of binocularity to visuomotor control also comes from examining motor performance in individuals with amblyopia, a condition characterized by reduced visual acuity and poor binocular function. Overall, research in this field has advanced our understanding of the role of binocular vision in the development and performance of visuomotor skills, the first step towards developing assessment tools and targeted rehabilitation for children with neurodevelopment disorders at risk of poor visuomotor outcomes.

This article is part of a discussion meeting issue ‘New approaches to 3D vision’.
Familiar size affects perception differently in virtual reality and the real world
Authors: Rzepka Anna M. , Hussey Kieran J. , Maltz Margaret V. , Babin Karsten , Wilcox Laurie M. , Culham Jody C.
Published: December 2022

The promise of virtual reality (VR) as a tool for perceptual and cognitive research rests on the assumption that perception in virtual environments generalizes to the real world. Here, we conducted two experiments to compare size and distance perception between VR and physical reality (Maltz
et al
. 2021
J. Vis.
21
, 1–18). In experiment 1, we used VR to present dice and Rubik's cubes at their typical sizes or reversed sizes at distances that maintained a constant visual angle. After viewing the stimuli binocularly (to provide vergence and disparity information) or monocularly, participants manually estimated perceived size and distance. Unlike physical reality, where participants relied less on familiar size and more on presented size during binocular versus monocular viewing, in VR participants relied heavily on familiar size regardless of the availability of binocular cues. In experiment 2, we demonstrated that the effects in VR generalized to other stimuli and to a higher quality VR headset. These results suggest that the use of binocular cues and familiar size differs substantially between virtual and physical reality. A deeper understanding of perceptual differences is necessary before assuming that research outcomes from VR will generalize to the real world.

This article is part of a discussion meeting issue ‘New approaches to 3D vision’.
Structure prediction-based insights into the patatin family of Mycobacterium tuberculosis
Authors: Ragavendran P.V. , Tripathi Vaishnavi , Gandotra Sheetal
Published: December 2022

Despite its genome sequencing more than two decades ago, the majority of the genes of

Mycobacterium tuberculosis

remain functionally uncharacterized. Patatins are one such class of proteins that, despite undergoing an expansion in this pathogenic species compared to their non-pathogenic cousins, remain largely unstudied. Recent advances in protein structure prediction using machine learning tools such as AlphaFold2 have provided high-confidence predicted structures for all

M. tuberculosis

proteins. Here we present detailed analyses of the patatin family of

M. tuberculosis

using AlphaFold-predicted structures, providing insights into likely modes of regulation, membrane interaction and substrate binding. Regulatory domains within this family of proteins include cyclic nucleotide binding, lid-like domains and other helical domains. Using structural homologues, we identified the likely membrane localization mechanisms and substrate-binding sites. These analyses reveal diversity in their regulatory capacity, mechanisms of membrane binding and likely length of fatty acid substrates. Together, this analysis suggests unique roles for the eight predicted patatins of

M. tuberculosis

.
Fusion of a bacterial cadherin-like domain and green fluorescent protein as a specific probe to study biofilm matrix formation in Rhizobium spp
Authors: Abdian Patricia L. , Malori María Soledad , Caramelo Julio J. , Checchi Abi Maglio , Russo Daniela M. , Zorreguieta Angeles , Berretta Marcelo F. , Benintende Graciela
Published: December 2022

Rhizobium

adhering proteins or ‘Raps’ are secreted proteins identified in a very restricted group of rhizobial strains, specifically those belonging to

R. leguminosarum

and

R. etli

. The distinctive feature of members of the Rap family is the presence of one or two cadherin-like domains or CHDLs that are also present in numerous extracellular bacterial and archaeal proteins and were proposed to confer carbohydrate binding ability. We have previously made an in-depth characterization of RapA2, a calcium-binding lectin, composed by two CHDLs, involved in biofilm matrix remodelling in

R. leguminosarum

bv. viciae 3841. In this study, CHDLs derived from RapA2 were analysed in detail, finding significant structural and functional differences despite their considerable sequence similarity. Only the carboxy-terminal CHDL retained properties similar to those displayed by RapA2. Our findings were used to obtain a novel fluorescent probe to study biofilm matrix development by confocal laser scanning microscopy, and also to shed some light on the role of the ubiquitous CHDL domains in bacterial secreted proteins.
Variability in the spatiotemporal propagation of interictal spikes on magnetoencephalography in temporal lobe epilepsy
Authors: Zhou Daniel J. , Gumenyuk Valentina , Taraschenko Olga , Grobelny Bartosz T. , Stufflebeam Steven M. , Peled Noam
Published: December 2022

Magnetoencephalography (MEG) is clinically used to help localize interictal spikes in discrete brain areas through the equivalent current dipole (ECD) method for patients with refractory epilepsy. The propagation of interictal spikes in adjacent regions was shown to be correlated with worse surgical outcomes in patients with temporal lobe epilepsy (TLE). Yet, the ECD method does not account for the temporal dynamics of spike activity, making it challenging to define the margins of the interictal network. Furthermore, the ECD results can be affected by states of arousal or sleep that alter background MEG activity.

In this study, we developed a module in the custom-built Multi-Modal Analysis and Visualization Tool (MMVT) that analyzes the spatiotemporal dynamics of interictal spikes and removes normal variations associated with sleep. We analyzed MEG data from seven TLE patients and characterized their interictal spatiotemporal dynamics. In all patients, the onset of interictal spike activity appeared near the determined site of the epileptogenic zone based on corresponding neuroimaging and EEG data. The propagated source activity by 10 ms ranged from near the region of onset to spreading to extratemporal regions, such as the frontal lobe or insula.

We demonstrated the feasibility of a novel method to assess the spatiotemporal properties of interictal spikes in patients with medically refractory TLE and to better delineate their onset and propagation patterns on MEG analysis. In doing so, we illustrate how variable the spike propagation distribution and speed may be within a 10 ms window. This visualization of the time component of the interictal networks offers an advantage over the currently used ECD method in characterizing the epileptic network and may help better guide surgical planning and provide for improved interventional outcomes in patients with TLE.
Amelioration of non-alcoholic fatty liver disease by targeting G protein-coupled receptor 110: A preclinical study
Authors: Wu Mengyao , Lo Tak-Ho , Li Liping , Sun Jia , Deng Chujun , Chan Ka-Ying , Li Xiang , Yeh Steve Ting-Yuan , Lee Jimmy Tsz Hang , Lui Pauline Po Yee , Xu Aimin , Wong Chi-Ming
Published: December 2022

Background

Recent research has shown that the G protein-coupled receptor 110 (GPR110) is an oncogene. The evidence mainly based on high expression of GPR110 in numerous cancer types; and knockdown GPR110 can reduced the cell migration, invasion, and proliferation. GPR110 is, however, mostly expressed in the liver of healthy individuals. The function of GPR110 in liver has not been revealed. Interestingly, expression level of hepatic GPR110 is dramatically decreased in obese subjects. Here, we examined whether GPR110 has a role in liver metabolism.

Methods

We used recombinant adeno-associated virus-mediated gene delivery system and antisense oligonucleotide to manipulate the hepatic GPR110 expression level in diet-induced obese mice to investigate the role of GPR110 in hepatic steatosis. The clinical relevance was examined using transcriptome profiling and archived biopsy specimens of liver tissues from non-alcoholic fatty liver disease (NAFLD) patients with different degree of fatty liver.

Results

The expression of GPR110 in the liver was directly correlated to fat content in the livers of both obese mice and NAFLD patients. Stearoyl-coA desaturase 1 (SCD1), a crucial enzyme in hepatic de novo lipogenesis, was identified as a downstream target of GPR110 by RNA-sequencing analysis. Treatment with the liver-specific SCD1 inhibitor MK8245 and specific shRNAs against SCD1 in primary hepatocytes improved the hepatic steatosis of GPR110-overexpressing mice and lipid profile of hepatocytes, respectively.

Conclusions

These results indicate GPR110 regulates hepatic lipid metabolism through controlling the expression of SCD1. Down-regulation of GPR110 expression can potentially serve as a protective mechanism to stop the over-accumulation of fat in the liver in obese subjects. Overall, our findings not only reveal a new mechanism regulation the progression of NALFD, but also proposed a novel therapeutic approach to combat NAFLD by targeting GPR110.

Fundings

This work was supported in part by National Natural Science Foundation of China 81870586 (CMW), 82270941 and 81974117 (JS), Area of Excellence AoE/M-707/18 (AX and CMW), and General Research Fund 15101520 (CMW).

Highlights

GPR110 regulates hepatic lipid metabolism.

High level of hepatic GPR110 aggravates the progression of NAFLD by inducing SCD1 expression.

Reduction in hepatic GPR110 is required to alleviate the progression of NAFLD.

Targeting hepatic GPR110 improves hepatic steatosis.
FDA approved Artificial Intelligence and Machine Learning (AI/ML)-Enabled Medical Devices: An updated landscape
Authors: Joshi Geeta , Jain Aditi , Araveeti Shalini Reddy , Adhikari Sabina , Garg Harshit , Bhandari Mukund
Published: December 2022

As artificial intelligence (AI) has been highly advancing in the last decade, machine learning (ML) enabled medical devices are increasingly used in healthcare. In this article, we performed comprehensive analysis of FDA approved Artificial Intelligence and Machine Learning (AI/ML)- Enabled Medical Devices and offer an in-depth analysis of clearance pathways, approval timeline, regulation type, medical specialty, decision type, recall history etc. We found a significant surge in approvals since 2018, with clear dominance of radiology specialty in the application of machine learning tools, attributed to the abundant data from routine clinical data. The study also reveals a reliance on the 510(k)-clearance pathway, emphasizing its basis on substantial equivalence and often bypassing the need for new clinical trials. Also, it notes an underrepresentation of pediatric- focused devices and trials, suggesting an opportunity for expansion in this demographic. Moreover, the geographical limitation of clinical trials, primarily within the United States, points to a need for more globally inclusive trails to encompass diverse patient demographics. This analysis not only maps the current landscape of AI/ML-Enabled Medical Devices but also pinpoints trends, potential gaps, and areas for future exploration, clinical trial practices, and regulatory approaches.
Few shot learning for phenotype-driven diagnosis of patients with rare genetic diseases
Authors: Alsentzer Emily , Li Michelle M. , Kobren Shilpa N. , Noori Ayush ,   Undiagnosed Diseases Network, Kohane Isaac S. , Zitnik Marinka
Published: December 2022

There are more than 7,000 rare diseases, some affecting 3,500 or fewer patients in the US. Due to clinicians’ limited experience with such diseases and the heterogeneity of clinical presentations, approximately 70% of individuals seeking a diagnosis today remain undiagnosed. Deep learning has demonstrated success in aiding the diagnosis of common diseases. However, existing approaches require labeled datasets with thousands of diagnosed patients per disease. Here, we present SHEPHERD, a few shot learning approach for multi-faceted rare disease diagnosis. SHEPHERD performs deep learning over a biomedical knowledge graph enriched with rare disease information to perform phenotype-driven diagnosis. Once trained, we show that SHEPHERD can provide clinical insights about real-world patients. We evaluate SHEPHERD on a cohort of N = 465 patients representing 299 diseases (79% of genes and 83% of diseases are represented in only a single patient) in the Undiagnosed Diseases Network. SHEPHERD excels at several diagnostic facets: performing causal gene discovery (causal genes are predicted at rank = 3.56 on average), retrieving “patients-like-me” with the same causal gene or disease, and providing interpretable characterizations of novel disease presentations. We additionally examine SHEPHERD on two other real-world cohorts, MyGene2 (N = 146) and Deciphering Developmental Disorders Study (N = 1,431). SHEPHERD demonstrates the potential of deep learning to accelerate rare disease diagnosis and has implications for using deep learning on medical datasets with very few labels.
Meta-analysis of atopic dermatitis in 1,094,060 individuals identifies new risk loci, and sub-analysis characterizes the loci with disease severity and onset
Authors: Pasanen Anu , Sliz Eeva , Huilaja Laura , FinnGen  ,   Estonian Biobank Research Team, Reimann Ene , Mägi Reedik , Laisk Triin , Tasanen Kaisa , Kettunen Johannes
Published: December 2022

Atopic dermatitis (AD) is a common inflammatory skin disease highly attributable to genetic factors. Here, we report results from a genome-wide meta-analysis of AD in 37,541 cases and 1,056,519 controls with data from the FinnGen project, the Estonian Biobank, the UK Biobank, the EAGLE Consortium, and the BioBank Japan. We detected 77 independent AD-associated loci of which 10 were novel. The associated loci showed enrichment in various immune regulatory processes. We further performed subgroup analyses of mild and severe AD, and of early and late-onset AD, with data from the FinnGen project. 55 of the 79 tested variants in the associated loci showed larger effect estimates for severe than mild AD as determined through administered treatment. The age of onset, as determined by the first hospital visit with AD diagnosis, was lower in patients with particular AD-risk alleles. Our findings add to the knowledge of the genetic background of AD and may underlay the development of new therapeutic strategies.
The effect of recognition on competition among clones in spatially structured microbial communities
Authors: Bingham Adrienna , Sur Aparajita , Shaw Leah B. , Murphy Helen A.
Published: December 2022

In spatially structured microbial communities, clonal growth of stationary cells passively generates clusters of related cells. This can lead to stable cooperation without the need for recognition mechanisms. However, recent research suggests that some biofilm-forming microbes may have mechanisms of kin recognition. To explore this unexpected observation, we studied the effects of different types of cooperation in a microbial colony using spatially explicit, agent-based simulations of two interacting strains. We found scenarios that favor a form of kin recognition in spatially structured microbial communities. In the presence of a “cheater” strain, strains with greenbeard cooperation was able to increase in frequency more than obligate cooperators. This effect was most noticeable in high density colonies and when the cooperators were not as abundant as the cheaters. We also studied whether a polychromatic greenbeard, in which cells only cooperate with their own type, could provide a numerical benefit beyond a simple, binary greenbeard. We found the greatest benefit to a polychromatic greenbeard when cooperation is highly effective. These results suggest that in some ecological scenarios, recognition mechanisms may be beneficial even in spatially structured communities.
Creating an Ignorance-Base: Exploring Known Unknowns in the Scientific Literature
Authors: Boguslav Mayla R. , Salem Nourah M. , White Elizabeth K. , Sullivan Katherine J. , Bada Michael , Hernandez Teri L. , Leach Sonia M. , Hunter Lawrence E.
Published: December 2022

Background

Scientific discovery progresses by exploring new and uncharted territory. More specifically, it advances by a process of transforming unknown unknowns first into known unknowns, and then into knowns. Over the last few decades, researchers have developed many knowledge bases to capture and connect the knowns, which has enabled topic exploration and contextualization of experimental results. But recognizing the unknowns is also critical for finding the most pertinent questions and their answers. Prior work on known unknowns has sought to understand them, annotate them, and automate their identification. However, no knowledge-bases yet exist to capture these unknowns, and little work has focused on how scientists might use them to trace a given topic or experimental result in search of open questions and new avenues for exploration. We show here that a knowledge base of unknowns can be connected to ontologically grounded biomedical knowledge to accelerate research in the field of prenatal nutrition.

Results

We present the first ignorance-base, a knowledge-base created by combining classifiers to recognize ignorance statements (statements of missing or incomplete knowledge that imply a goal for knowledge) and biomedical concepts over the prenatal nutrition literature. This knowledge-base places biomedical concepts mentioned in the literature in context with the ignorance statements authors have made about them. Using our system, researchers interested in the topic of vitamin D and prenatal health were able to uncover three new avenues for exploration (immune system, respiratory system, and brain development), which were buried among the many standard enriched concepts, by searching for concepts enriched in ignorance statements. Additionally, we used the ignorance-base to enrich concepts connected to a gene list associated with vitamin D and spontaneous preterm birth and found an emerging topic of study (brain development) in an implied field (neuroscience). The researchers could look to the field of neuroscience for potential answers to the ignorance statements.

Conclusion

Our goal is to help students, researchers, funders, and publishers better understand the state of our collective scientific ignorance (known unknowns) in order to help accelerate research through the continued illumination of and focus on the known unknowns and their respective goals for scientific knowledge.

Graphical Abstract

Highlights

We created the first ignorance-base (knowledge-base) to capture goals for scientific knowledge

Our exploration methods provide analyses, summaries, and visualizations based on a query

Ignorance enrichment provided fruitful avenues for future research

Exploration by topic in vitamin D found three avenues to explore

Exploration by experimental results for vitamin D and preterm birth found an emerging topic
HLApollo: A superior transformer model for pan-allelic peptide-MHC-I presentation prediction, with diverse negative coverage, deconvolution and protein language features
Authors: Thrift William John , Lounsbury Nicolas W. , Broadwell Quade , Heidersbach Amy , Freund Emily , Abdolazimi Yassan , Phung Qui T , Chen Jieming , Capietto Aude-Hélène , Tong Ann-Jay , Rose Christopher M. , Blanchette Craig , Lill Jennie R , Haley Benjamin , Delamarre Lélia , Bourgon Richard , Liu Kai , Jhunjhunwala Suchit
Published: December 2022

Antigen presentation on MHC class I (MHC-I) is key to the adaptive immune response to cancerous cells. Computational prediction of peptide presentation by MHC-I has enabled individualized cancer immunotherapies. Here, we introduce HLApollo, a transformer-based approach with end-to-end modeling of MHC-I sequence, deconvolution, and flanking sequences. To achieve this, we develop a novel training strategy, negative set switching, which greatly reduces overfitting to falsely presumed negatives that are necessarily found in presentation datasets. HLApollo shows a meaningful improvement compared to recent MHC-I models on peptide presentation (20.19% average precision (AP)) and immunogenicity (4.1% AP). As expected, adding gene expression boosts the performance of HLApollo. More interestingly, we show that introduction of features from a protein language model, ESM 1b, remarkably recoups much of the benefits of gene expression in absence of true expression measurements. Finally, we demonstrate excellent pan-allelic generalization, and introduce a framework for estimating the expected accuracy of HLApollo for untrained alleles. This guides the use of HLApollo in a clinical setting, where rare alleles may be observed in some subjects, particularly for underrepresented minorities.