bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Nature-Themed Recharge Room on Healthcare Workers' Level of Stress and Anxiety
Authors: Besa Rocel , Angelo Ellen , Cutroneo Annamarie , Frieman Amy , Paliwal Mani , Williams Dawn
Published: August 2023

OBJECTIVE

To determine if there is a difference in stress and anxiety before and after the use of the nature-themed recharge room.

BACKGROUND

Psychological support measures have been noted to be relevant to nurses; however, the effect of the pandemic on the healthcare workers' emotional and psychological well-being led to urgent calls to implement psychological support measures more widely.

METHODS

The study utilized a 1-group pretest and posttest design. One hundred sixty hospital employees utilized the recharge room, with 131 completed questionnaires counted in the data analysis. Data were collected using the demographic form, Perceived Stress Scale, and State-Trait Anxiety Inventory.

RESULTS

Most participants were between 25 and 35 years old, female, worked the morning shift, had 3 to 5 years of experience, preferred a water feature theme, and used the room for 10 minutes. The mean stress preintervention score was 7.44, and postintervention score was 7.17, with the difference not statistically significant. The mean anxiety preintervention score was 14.17, and postintervention score was 8.48, with the difference statistically significant at a P < 0.05. Females working in the hospital for 1 to 5 years were physicians/residents, nursing support staff, and leaders with the highest mean stress (4-item Perceived Stress Scale) and anxiety (6-item State-Trait Anxiety Inventory) preintervention scores. Comparing the preintervention and postintervention anxiety levels, the highest reduction was noted among females working in the hospital for 1 to 3 years and nursing support staff who have used the room for 5 to 15 minutes with 2 or fewer people.

CONCLUSION

Organizational leaders should offer psychological support programs, such as the nature-themed recharge room, to help reduce the healthcare workers' stress and anxiety.
Health System-Academic Partnerships
Authors: Kapu April N. , McCamey Danielle
Published: August 2023

This month's column highlights the importance of established health system academic partnerships in strengthening the advanced practice RN workforce.
Behçet Disease and Bipolar Disorder: A Case Report and Review
Authors: Mota Freitas Rodrigo Ferreira da , Guerra Ana Pestana Boavida Monteiro
Published: August 2023

Behçet disease (BD) is a rare, multifactorial condition with multiple manifestations affecting various systems. Bipolar disorder has been reported as more frequent in individuals with BD than in the general population. We report a case of BD and bipolar disorder and summarize previous findings in the literature concerning this topic. Our case illustrates the relevance of managing comorbid BD and bipolar disorder. It is crucial to manage both conditions to maximize the patient’s quality of life. Clinicians should be aware of the risk of bipolar disorder in patients with BD and vice versa and an integrated model of care could be useful. The exact biological and psychological aspects mediating the association between the 2 diagnoses remain unclear. Further, larger, prospective studies could help better clarify this relationship, leading to new advances in diagnosis and treatment.
Safety and Efficacy of a Central Pedicle Technique for Mastopexy and Mastopexy with Implant Augmentation
Authors: Orloff George
Published: August 2023

Background:

The central pedicle technique (CPT) is rarely used to perform mastopexy or mastopexy with implant augmentation despite having robust perfusion and allowing for great exposure, resulting in reproducible results. This study was conducted to review one surgeon’s experience using the CPT for both mastopexy and mastopexy with implant augmentation.

Method:

A retrospective review of consecutive patients who had a mastopexy or mastopexy with augmentation using a standardized CPT from 2017 through 2021 was performed.

Results:

A total of 201 patients were identified for inclusion: 120 had a bilateral central pedicle mastopexy, 75 had bilateral central pedicle mastopexy and implants, and 6 had unilateral central pedicle mastopexy with implants because of asymmetry. Mean follow-up was 11.2 months. The average age was 45.4 years, body mass index 25.1 kg/m², and implant size 275 cc. The overall complication rate was 9.5%: 9.2% for CPT mastopexy and 9.9% for CPT mastopexy with implants. No revisional surgery was requested. None of the patients experienced nipple or skin necrosis.

Conclusions:

This study demonstrates that CPT mastopexy with or without an implant can be performed safely with a low complication rate. Additional benefits include standardized markings before surgery, visualization of the entire breast mound, and reliable perfusion. The technique excels in correcting asymmetry. CPT mastopexy with or without an implant is a safe and effective option for the treatment of breast ptosis.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Radial and Ulnar Forearm Free Flaps: A Critical Comparison of Donor-Site Morbidity and Its Impact on Quality of Life
Authors: Al-Aroomi Maged Ali , Duan Weiyi , Al-Worafi Naseem Ali , Al-Moraissi Essam Ahmed , Mashrah Mubarak Ahmed , Liu Minda , Xue Xiaomeng , Sun Changfu
Published: August 2023

Background:

A poor evidence basis exists regarding directly comparing objective and subjective donor-site morbidity associated with the forearm flap. The authors evaluated the postoperative donor-site complications and quality-of-life outcomes between the radial forearm free flap (RFFF) and the ulnar forearm free flap (UFFF).

Methods:

All patients undergoing RFFF or UFFF harvest were included. Grip strength, pinch strength, wrist range of movement, and testing of skin sensitivity were assessed with the appropriate scales at different time intervals. In addition, appearance and quality of life were assessed using the Patient and Observer Scar Assessment Scale and the Disabilities of Arm, Shoulder, and Hand instruments.

Results:

Eighty patients were enrolled (RFFF, n = 40; and UFFF, n = 40). A short-term reduction in grip strength, fine motor skills (tip pinch, key pinch, palmar pinch), and range of motion was observed for the RFFF group and improved over time. None of the patients in either group experienced functional disturbance in grip strength, wrist motion, fine motor skills, or sensation to light touch at 1 year. Nine patients experienced partial skin graft loss (RFFF, n = 6; UFFF, n = 3). There was a significantly higher incidence of temporary numbness in the RFFF group (P = 0.040). Persistent numbness occurred in 3 cases in the RFFF group. Cold intolerance was significantly lower in the UFFF group (2.5%) than in RFFF group (22.5%). Moreover, the mean Patient and Observer Scar Assessment Scale and Disabilities of Arm, Shoulder, and Hand scores were reduced at 12 months compared with 6 months, significantly superior for UFFF.

Conclusions:

Objective function limitations are reversible short-term effects after forearm flap and do not affect daily routines in the long term. In addition, UFFF appears to be preferred over RFFF for subjective outcomes, which emphasizes that UFFF should be considered as an alternative to RFFF for reconstructing soft-tissue defects.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Study on the Application of Concentrated Growth Factor Combined With Adipose Transplantation in Repairing Depressed Deformities of Soft Tissue in the Face
Authors: Li Honghong , Yang Zhiguo , Lou Yin , Bao Qiong , Xie Juan , Cao Dongsheng
Published: August 2023

Background

Autologous fat is a rich source of adipose tissue that is safe for transplantation. Decreasing the long-term absorption rate is key to improve the survival of transplanted adipose tissue. The aim of this study was to assess the effect of concentrated growth factor (CGF) on the survival of transplanted adipose tissue for repair of facial depression malformations.

Methods

Coleman adipose granules (CAGs) were prepared from venous blood. In the animal experiment, the ears of 30 healthy male New Zealand white rabbits were randomly allocated to 1 of 4 groups: CGF + CAG (CGF group), platelet-rich fibrin (PRF) + CAG (PRF group), CAG alone (CAG group), and adipose granule transplantation group (control group). Postoperative survival of the transplanted adipose tissue was assessed, the survival and absorption rates of adipose were calculated, and immunohistochemical analysis of specimens was conducted by staining with hematoxylin and eosin and Oil Red O. Of 43 outpatients, 22 received simple adipose transplantation and 21 received autologous CGF combined with adipose transplantation. The adipose absorption rate, complication rate, and cosmetic improvement of the 2 groups were compared.

Results

More adipocytes that are normal were observed in the CGF group, with fewer vacuoles and more uniform distribution of adipose tissue. Survival of the adipose tissue was superior in the CGF and PRF groups. Meanwhile, vascular density and long-term stability were better in the CGF group than the PRF group. In terms of clinical efficacy, the uniformity and survival rate of the adipose tissue were relatively improved in the CGF group compared with the simple adipose particle transplantation group, with less early liquefaction.

Conclusion

Concentrated growth factor stabilized and improved the survival of transplanted adipose tissue for filling of facial depression malformations.
Reconstruction of Medial Orbital Wall Using Autologous Perpendicular Plate of Ethmoid
Authors: Zhang Shiyong , Xu Zhihua , Zhang Xiaoqing , Wang Xinhua , Ye Rui
Published: August 2023

The aim of this study is to investigate the feasibility of perpendicular plate of ethmoid as material for the reconstruction of medial orbital wall. The main outcome measurement was preoperative and postoperative orbital volume. The authors performed a study including 17 patients who have isolated medial orbital wall fracture (blow-out fracture). All the patients were fixed the defect using autologous perpendicular plate of ethmoid under endonasal approach. The authors compared the preoperative and postoperative orbital volume difference (unaffected orbit, affected orbit) of all the patients, and observed the improvement of diplopia or ocular motility disorders after operation. All 17 medial orbital wall reconstruction surgeries were successful with no severe postoperative ophthalmic complications. Statistically significant differences were found between the preoperative and postoperative orbital tissue volumes for the affected orbit. There was no statistically significant difference found between the tissue volume of the contralateral unaffected orbit and the affected orbit after reconstruction. And postoperative computed tomography showed the implant is in place and there is no medial rectus incarceration. Autologous perpendicular plate of ethmoid proved to be safe and effective in the reconstruction of medial orbital wall under endonasal approach with cost-effectivence, low complication rate, high biocompatibility, and minimally invasion.
Restoration of the Lateral Canthus and Stabilization of the Lower Eyelid After Failed Esthetic Lateral Canthoplasty
Authors: Zhang Li , Chen Yue , Li Yang , Li Dongmei
Published: August 2023

Background:

An improper procedure of esthetic lateral canthoplasty can lead to lateral canthal deformity with other complications. To ensure proper canthal contour and eyelid function, the lateral canthus must be restored and the lower eyelid must be stabilized.

Methods:

This was a retrospective study that included a group of consecutive patients who had failed esthetical lateral canthoplasty between 2020 and 2022. All patients underwent the modified lateral tarsal strip procedure to restore the normal anatomy of the lateral canthus and stabilize the lower eyelid. Clinical data (age, sex, laterality, follow-up, ocular symptoms, previous medical history, and lateral canthal deformity) were collected. Preoperative and postoperative photographs were analyzed for cosmetic outcomes.

Results:

Among the 15 female patients, 25 eyelids were treated, including both eyes in 10 patients and only the left eye in 5 others. The mean age was 32.6 years. The mean follow-up was 13.34 months. All the patients had undergone esthetic lateral canthoplasty with other esthetic surgeries. Lateral canthus deformities include canthal webbing, rounding canthus, eyelid margin defect, remnant raw surface, mucosal exposure, lower eyelid retraction, sclera show, ectropion, symblepharon, and lagophthalmos. All the patients exhibited esthetically satisfactory results with improved ocular symptoms. In statistical analysis, horizontal palpebral aperture, vertical palpebral aperture, MRD2, and lateral canthus angle were statistically different pre to postprocedure (paired t test, P < 0.001).

Conclusions:

Restoration of the lateral canthus and stabilization of the lower eyelid using the modified lateral tarsal strip procedure showed good functional and cosmetic outcomes in patients who had failed lateral canthoplasty.
Bone Tissue Engineering (BTE) of the Craniofacial Skeleton, Part II: Translational Potential of 3D-Printed Scaffolds for Defect Repair
Authors: Slavin Blaire V. , Nayak Vasudev V. , Boczar Daniel , Bergamo Edmara TP , Slavin Benjamin R. , Yarholar Lauren M. , Torroni Andrea , Coelho Paulo G. , Witek Lukasz
Published: August 2023

Computer-aided design/computer-aided manufacturing and 3-dimensional (3D) printing techniques have revolutionized the approach to bone tissue engineering for the repair of craniomaxillofacial skeletal defects. Ample research has been performed to gain a fundamental understanding of the optimal 3D-printed scaffold design and composition to facilitate appropriate bone formation and healing. Benchtop and preclinical, small animal model testing of 3D-printed bioactive ceramic scaffolds augmented with pharmacological/biological agents have yielded promising results given their potential combined osteogenic and osteoinductive capacity. However, other factors must be evaluated before newly developed constructs may be considered analogous alternatives to the “gold standard” autologous graft for defect repair. More specifically, the 3D-printed bioactive ceramic scaffold’s long-term safety profile, biocompatibility, and resorption kinetics must be studied. The ultimate goal is to successfully regenerate bone that is comparable in volume, density, histologic composition, and mechanical strength to that of native bone. In vivo studies of these newly developed bone tissue engineering in translational animal models continue to make strides toward addressing regulatory and clinically relevant topics. These include the use of skeletally immature animal models to address the challenges posed by craniomaxillofacial defect repair in pediatric patients. This manuscript reviews the most recent preclinical animal studies seeking to assess 3D-printed ceramic scaffolds for improved repair of critical-sized craniofacial bony defects.
Three-Dimensional Anthropometry for Evaluating Philtrum Contour in Patients With Unilateral Cleft Lip: Comparison Between Photographic Assessment and 3-Dimensional Anthropometry
Authors: Park Hojin , Min Jaechung , Koh Kyung S.
Published: August 2023

Philtrum reconstruction in patients with unilateral cleft lip is a major concern in cheiloplasty. Moreover, a quantitative evaluation of the philtrum contour has not been possible. Advances in 3-dimensional (3D) imaging technology have enabled highly accurate assessments of facial surfaces. This study aimed to justify using 3D anthropometric measurements to quantify traditional photographic grading systems. Sixty-six children with unilateral cleft lip, aged 4 to 6 years (mean age: 69.1±5.7 mo), who visited the outpatient clinic from January to December 2020 were included. A plastic surgeon panel graded the philtrum contour using digital photographs, and 3D anthropometry was performed using a 3D imaging system. The philtrum height, philtrum height difference, and dimple depth were measured at the middle of the philtrum. The philtrum height did not show significant changes across the photographic scores (P=0.06), whereas noticeable differences were observed in the dimple depths based on photographic scores (P<0.001). The correlation analysis revealed the highest correlation between the photographic score and dimple depth (rho=0.897, P<0.001). The philtrum height on the cleft side (rho=0.478, P<0.001) also correlated with the photographic score, but the correlation was weaker than that of the dimple depth. The dimple depth and philtrum height can help define the philtrum contour. Furthermore, the dimple depth reflects the philtrum contour better and is more suitable as a single parameter. However, relying on a single philtrum height measurement may be insufficient for reliable evaluations, as the relative height from the surrounding tissues is more important than the absolute height measured using 3D anthropometry.
Secondary Reconstruction of Late Deformities of the Orbitozygomaticomaxillary Complex using a Halo Device
Authors: Nuri Takashi , Asaka Akinori , Ueda Koichi
Published: August 2023

Reconstructing late deformities of the orbitozygomaticomaxillary complex after inadequate treatment of facial fractures requires zygomatic osteotomy to reposition the bony fragments to their anatomical position. However, confirming the position of the bone fragments can be challenging due to the loss of anatomic landmarks caused by bone remodeling, and swelling resulting from surgery, which might hinder locating the bone from the body surface. Here, the authors describe fixation of the halo of the Blue Device multi-vector distraction system to the patient’s ear canal, with alignment of the position of the zygoma by measuring the distances between the halo and zygoma using several reference points. This technique allows for measurement not only from the body surface using a K-wire but also directly to the bone using a needle. The authors applied this technique in 2 cases of post-traumatic deformities after complex zygomatic fractures. Both cases achieved an almost symmetrical appearance of the infraorbital region.
Automated Cephalometric Landmark Detection Using Deep Reinforcement Learning
Authors: Hong Woojae , Kim Seong-Min , Choi Joongyeon , Ahn Jaemyung , Paeng Jun-Young , Kim Hyunggun
Published: August 2023

Accurate cephalometric landmark detection leads to accurate analysis, diagnosis, and surgical planning. Many studies on automated landmark detection have been conducted, however reinforcement learning-based networks have not yet been applied. This is the first study to apply deep Q-network (DQN) and double deep Q-network (DDQN) to automated cephalometric landmark detection to the best of our knowledge. The performance of the DQN-based network for cephalometric landmark detection was evaluated using the IEEE International Symposium of Biomedical Imaging (ISBI) 2015 Challenge data set and compared with the previously proposed methods. Furthermore, the clinical applicability of DQN-based automated cephalometric landmark detection was confirmed by testing the DQN-based and DDQN-based network using 500-patient data collected in a clinic. The DQN-based network demonstrated that the average mean radius error of 19 landmarks was smaller than 2 mm, that is, the clinically accepted level, without data augmentation and additional preprocessing. Our DQN-based and DDQN-based approaches tested with the 500-patient data set showed the average success detection rate of 67.33% and 66.04% accuracy within 2 mm, respectively, indicating the feasibility and potential of clinical application.
Avoiding Inferior Alveolar Nerve Injury During Sagittal Split Ramus Osteotomy
Authors: Hattori Yoshitsugu , Murali Srinisha P. , Lo Lun-Jou
Published: August 2023

Orthognathic surgery is highly effective in improving overall facial esthetics, in addition to achieving an ideal occlusion. Sagittal split ramus osteotomy (SSRO) of the mandible is the mainstay of modern orthognathic surgery, but intraoperative injury to the inferior alveolar nerve (IAN) remains one of the common complications. The authors report a case of 19-year-old male patient with left cleft lip and palate who received orthognathic surgery involving SSRO. The patient’s right IAN ran close to the outer cortex of the mandible, but SSRO was successfully performed without injuring the nerve. Detailed preoperative evaluation using computed tomography images is essential. Blind splitting maneuvers during SSRO may cause IAN injury, and direct visualization inside the ramus helps to prevent injury to the nerve. Sagittal split ramus osteotomy could be considered as a viable option even when the IAN runs close to the outer cortex. This article describes SSRO procedures, highlighting the methods to avoid nerve injury.
Deep learning-based risk stratification of preoperative breast biopsies using digital whole slide images
Authors: Boissin Constance , Wang Yinxi , Sharma Abhinav , Weitz Philippe , Karlsson Emelie , Robertson Stephanie , Hartman Johan , Rantalainen Mattias
Published: August 2023

Introduction

Nottingham histological grade (NHG) is a well established prognostic factor in breast cancer histopathology. However, manual NHG assessment of biopsies is challenging and has a large inter-assessor variability with a large proportion being classified as NHG2 (intermediate grade). Here, we evaluate whether DeepGrade, a previously developed model for the risk stratification of resected tumour specimens, could be applied to risk-stratify biopsy specimens.

Methods

A total of 11,943,905 tiles from 1171 whole slide images (WSIs) of preoperative biopsies from 897 patients diagnosed with breast cancer in Stockholm, Sweden, were included in this retrospective observational study. DeepGrade, a deep convolutional neural network model, was applied for classification of low and high risk tumours and evaluated against clinically assigned grades 1 and 3 using area under the operating curve (AUC). The prognostic value of the DeepGrade model in the biopsy setting was evaluated using time-to-event analysis.

Results

The DeepGrade model classified resected tumour cases with grades NHG1 and NHG3 using only biopsy specimens with an AUC of 0.903 (95% CI: 0.88;0.93). The model could also classify the biopsy NHG (1 and 3) assessed on the biopsy of 186 patients with an AUC of 0.959 (95% CI: 0.93; 0.99). Furthermore, out of the 434 NHG2 tumours, 255 (59%) were classified as DeepGrade2-low, and 179 (41%) were classified as DeepGrade2-high. Using a multivariable Cox proportional hazards model the hazard ratio between low- and high-risk groups was estimated as 2.01 (p-value = 0.036).

Conclusions

DeepGrade could predict the resected tumour grades NHG1 and NHG3 using only the biopsy specimen and sub-classify grade 2 tumours into low and high risks. The results demonstrate that the DeepGrade model can provide decision support for biopsy grading, and potentially provide decision support in the clinical setting to identifying high-risk tumours based on preoperative breast biopsies, thus improving information available for clinical treatment decisions.
SARS-CoV-2 shedding and evolution in immunocompromised hosts during the Omicron period: a multicenter prospective analysis
Authors: Raglow Zoe , Surie Diya , Chappell James D. , Zhu Yuwei , Martin Emily T. , Kwon Jennie H. , Frosch Anne E. , Mohamed Amira , Gilbert Julie , Bendall Emily E. , Bahr Auden , Halasa Natasha , Talbot H. Keipp , Grijalva Carlos G. , Baughman Adrienne , Womack Kelsey N. , Johnson Cassandra , Swan Sydney A. , Koumans Emilia , McMorrow Meredith L. , Harcourt Jennifer L. , Atherton Lydia J. , Burroughs Ashley , Thornburg Natalie J. , Self Wesley H. , Lauring Adam S.
Published: August 2023

Background

Prolonged SARS-CoV-2 infections in immunocompromised hosts may predict or source the emergence of highly mutated variants. The types of immunosuppression placing patients at highest risk for prolonged infection and associated intrahost viral evolution remain unclear.

Methods

Adults aged ≥18 years were enrolled at 5 hospitals and followed from 4/11/2022 – 2/1/2023. Eligible patients were SARS-CoV-2-positive in the previous 14 days and had a moderate or severely immunocompromising condition or treatment. Nasal specimens were tested by rRT-PCR every 2–4 weeks until negative in consecutive specimens. Positive specimens underwent viral culture and whole genome sequencing. A Cox proportional hazards model was used to assess factors associated with duration of infection.

Results

We enrolled 150 patients with: B cell malignancy or anti-B cell therapy (n=18), solid organ or hematopoietic stem cell transplant (SOT/HSCT) (n=59), AIDS (n=5), non-B cell malignancy (n=23), and autoimmune/autoinflammatory conditions (n=45). Thirty-eight (25%) were rRT-PCR-positive and 12 (8%) were culture-positive ≥21 days after initial SARS-CoV-2 detection or illness onset. Patients with B cell dysfunction had longer duration of rRT-PCR- positivity compared to those with autoimmune/autoinflammatory conditions (aHR 0.32, 95% CI 0.15-0.64). Consensus (>50% frequency) spike mutations were identified in 5 individuals who were rRT-PCR-positive >56 days; 61% were in the receptor-binding domain (RBD). Mutations shared by multiple individuals were rare (<5%) in global circulation.

Conclusions

In this cohort, prolonged replication-competent Omicron SARS-CoV-2 infections were uncommon. Within-host evolutionary rates were similar across patients, but individuals with infections lasting >56 days accumulated spike mutations, which were distinct from those seen globally.
Comparative neuroimaging of sex differences in human and mouse brain anatomy
Authors: Guma Elisa , Beauchamp Antoine , Liu Siyuan , Levitis Elizabeth , Ellegood Jacob , Pham Linh , Mars Rogier B , Raznahan Armin , Lerch Jason P
Published: August 2023

In vivo neuroimaging studies have established several reproducible volumetric sex differences in the human brain, but the causes of such differences are hard to parse. While mouse models are useful for understanding the cellular and mechanistic bases of sex-biased brain development in mammals, there have been no attempts to formally compare mouse and human sex differences across the whole brain to ascertain how well they translate. Addressing this question would shed critical light on use of the mouse as a translational model for sex differences in the human brain and provide insights into the degree to which sex differences in brain volume are conserved across mammals. Here, we use cross-species structural magnetic resonance imaging to carry out the first comparative neuroimaging study of sex-biased neuroanatomical organization of the human and mouse brain. In line with previous findings, we observe that in humans, males have significantly larger and more variable total brain volume; these sex differences are not mirrored in mice. After controlling for total brain volume, we observe modest cross-species congruence in the volumetric effect size of sex across 60 homologous brain regions (r=0.30; e.g.: M>F amygdala, hippocampus, bed nucleus of the stria terminalis, and hypothalamus and F>M anterior cingulate, somatosensory, and primary auditory cortices). This cross-species congruence is greater in the cortex (r=0.33) than non-cortex (r=0.16). By incorporating regional measures of gene expression in both species, we reveal that cortical regions with greater cross-species congruence in volumetric sex differences also show greater cross-species congruence in the expression profile of 2835 homologous genes. This phenomenon differentiates primary sensory regions with high congruence of sex effects and gene expression from limbic cortices where congruence in both these features was weaker between species. These findings help identify aspects of sex-biased brain anatomy present in mice that are retained, lost, or inverted in humans. More broadly, our work provides an empirical basis for targeting mechanistic studies of sex-biased brain development in mice to brain regions that best echo sex-biased brain development in humans.
Multi-scale model of axonal and dendritic polarization by transcranial direct current stimulation in realistic head geometry
Authors: Aberra Aman S. , Wang Ruochen , Grill Warren M. , Peterchev Angel V.
Published: August 2023

1.

Background

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation modality that can alter cortical excitability. However, it remains unclear how the subcellular elements of different neuron types are polarized by specific electric field (E-field) distributions.

Objective

To quantify neuronal polarization generated by tDCS in a multi-scale computational model.

Methods

We embedded layer-specific, morphologically-realistic cortical neuron models in a finite element model of the E-field in a human head and simulated steady-state polarization generated by conventional primary-motor-cortex–supraorbital (M1–SO) and 4×1 high-definition (HD) tDCS. We quantified somatic, axonal, and dendritic polarization of excitatory pyramidal cells in layers 2/3, 5, and 6, as well as inhibitory interneurons in layers 1 and 4 of the hand knob.

Results

Axonal and dendritic terminals were polarized more than the soma in all neurons, with peak axonal and dendritic polarization of 0.92 mV and 0.21 mV, respectively, compared to peak somatic polarization of 0.07 mV for 1.8 mA M1–SO stimulation. Both montages generated regions of depolarization and hyperpolarization beneath the M1 anode; M1–SO produced slightly stronger, more diffuse polarization peaking in the central sulcus, while 4×1 HD produced higher peak polarization in the gyral crown. Simulating polarization by uniform local E-field approximated the spatial distribution of tDCS polarization but produced large errors in some regions.

Conclusions

Polarization of pre- and postsynaptic compartments of excitatory and inhibitory cortical neurons may play a significant role in tDCS neuromodulation. These effects cannot be predicted from the E-field distribution alone but rather require calculation of the neuronal response.
Conditioned pain modulation of pressure pain is associated with reduced activation in the parietal operculum and posterior insula
Authors: Ojala Karita E. , Chu Ying , Finsterbusch Jürgen , Büchel Christian
Published: August 2023

Conditioned pain modulation (CPM) is the phenomenon of pain inhibiting further pain. CPM is impaired in patients suffering from various chronic pain conditions and may resemble a pro-nociceptive profile. A possible neural mechanism for CPM is descending control from cortical regions via brainstem that modulates neural activity at the level of the dorsal horn of the spinal cord where noxious input first arrives. We studied the involvement of the descending pain modulatory pathway by simultaneous functional imaging of the brain, brainstem, rostral medulla, and cervical spinal cord during CPM with pressure cuff algometry in 42 healthy human participants. Subjective CPM as measured by decreased pain ratings developed over the experiment with application of repeated short test stimuli for long conditioning pain compared with non-painful conditioning. Test stimuli paired with painful conditioning were associated with decreased BOLD fMRI activity in the parietal operculum (secondary somatosensory cortex) and posterior insula, as well as increased responses in bilateral primary somatosensory cortices. Subjective CPM reflected in pain ratings was associated with decreased test stimulus responses in somatosensory and pain-responsive brain regions such as the anterior and posterior insula and the parietal operculum. Conditioning pain and test pain were associated with increased neural activity in stimulus-ipsilateral spinal cord dorsal horn at segment C6 and C4, respectively. No evidence for neural correlates of CPM or associations with subjective CPM was observed in the spinal cord. Functional connectivity between the brain and spinal cord was altered during both conditioning and test pain but did not depend on conditioning intensity. Taken together, we observed neural activity associated with both negative (CPM) and positive modulation of pain in different somatosensory and pain-associated brain regions, and an association of these and other neural responses with subjective CPM. While we found that painful stimuli altered the connectivity along the descending pain modulatory pathway, we did not find evidence for a modulation by conditioning intensity nor neural correlates of CPM in the spinal cord.
Green Index: a widely accessible method to quantify greenness of photosynthetic organisms
Authors: Signorelli Santiago , Casaretto Esteban , Millar A. Harvey
Published: August 2023

Plant phenotyping involves the quantitative determination of complex plant traits using image analysis. One important parameter is how green plant tissues appear to the observer, which is indicative of their health and developmental stage. Various formulas have been developed to quantify this by calculating leaf greenness scores. We have developed a revised formula called “Green Index” (GI) devised out of the need to quantitatively assess how the apparent greenness of seedlings changes during de-etiolation. The GI calculation is simple, uses widely available RGB values of pixels in images as input, and does not require commercial software platforms or advanced computational skills. In this study we describe the conception of the GI formula, compare it with other widely used greenness formulas, and test its wider application in plant phenotyping using the open source free software platform RawTherapee. We demonstrate the utility of the GI in addressing common issues encountered in assessing plant biology experiments, underscoring its potential as a reliable and accessible tool. Finally, we explore the correlation between GI and chlorophyll content, assess its reliance on different types of photography, and summarizes the key steps for its effective utilization.
Considerations for the use of laboratory-based and field-based estimates of environmental tolerance in water management decisions for an endangered salmonid
Authors: Zeug Steven C. , Constandache Alex , Cavallo Bradley , Sciences Cramer Fish
Published: August 2023

Water infrastructure development and operation provides essential functions for human economic activity, health, and safety, yet this infrastructure can impact native fish populations resulting in legal protections that can, in turn, alter operations. Conflict over water allocation for ecological function and human use has come to the forefront at Shasta Reservoir, the largest water storage facility in California, USA. Shasta Reservoir supports irrigation for a multibillion-dollar agricultural industry, provides water for urban and domestic use, provides flood protection for downstream communities, and power generation as part of the larger Central Valley Project in California. Additionally, an endangered run of Chinook Salmon relies on cold water management at the dam for successful spawning and egg incubation. Tradeoffs between these uses can be explored through application of models that assess biological outcomes associated with flow and temperature management scenarios. However, the utility of models for management decisions are contingent on their characteristics, data used to construct them, and data collected to evaluate their predictions. We evaluated laboratory and field data currently available to parameterize temperature-egg survival models for winter run Chinook Salmon that are used to inform Shasta Dam operations. Models based on both laboratory and field data types had poor predictive performance which limits their value for management decisions. The sources of uncertainty that led to poor performance were different for each data type (field or laboratory) but were rooted in the fact that neither data set was collected with the intention to be used in a predictive model. Our findings suggest that if a predictive model is desired to evaluate operational tradeoffs, data must be collected for the specific variables desired, over an appropriate range of values, and at sufficient frequency to achieve the needed level of precision to address the modeling objective.
Domain-PFP: Protein Function Prediction Using Function-Aware Domain Embedding Representations
Authors: Ibtehaz Nabil , Kagaya Yuki , Kihara Daisuke
Published: August 2023

Domains are functional and structural units of proteins that govern various biological functions performed by the proteins. Therefore, the characterization of domains in a protein can serve as a proper functional representation of proteins. Here, we employ a self-supervised protocol to derive functionally consistent representations for domains by learning domain-Gene Ontology (GO) co-occurrences and associations. The domain embeddings we constructed turned out to be effective in performing actual function prediction tasks. Extensive evaluations showed that protein representations using the domain embeddings are superior to those of large-scale protein language models in GO prediction tasks. Moreover, the new function prediction method built on the domain embeddings, named Domain-PFP, significantly outperformed the state-of-the-art function predictors. Additionally, Domain-PFP demonstrated competitive performance in the CAFA3 evaluation, achieving overall the best performance among the top teams that participated in the assessment.
α-Synuclein emulsifies TDP-43 prion-like domain – RNA liquid droplets to promote heterotypic amyloid fibrils
Authors: Dhakal Shailendra , Mondal Malay , Mirzazadeh Azin , Banerjee Siddhartha , Ghosh Ayanjeet , Rangachari Vijayaraghavan
Published: August 2023

Many neurodegenerative diseases including frontotemporal lobar degeneration (FTLD), Lewy body disease (LBD), multiple system atrophy (MSA), etc., show colocalized deposits of TDP-43 and α-synuclein (αS) aggregates. To understand whether these colocalizations are driven by specific molecular interactions between the two proteins, we previously showed that the prion-like C-terminal domain of TDP-43 (TDP-43PrLD) and αS synergistically interact to form neurotoxic heterotypic amyloids in homogeneous buffer conditions. However, it remains unclear whether and how αS modulates TDP-43 present within liquid droplets and biomolecular condensates called stress granules (SGs). Here, using cell culture and in vitro TDP-43PrLD – RNA liquid droplets as models along with microscopy, nanoscale spatially-resolved spectroscopy, and other biophysical analyses, we uncover the interactions of αS with phase-separated droplets. We learn that αS acts as a Pickering agent by forming clusters on the surface of TDP-43PrLD – RNA droplets and emulsifying them. The ‘hardening’ of the droplets that follow by αS aggregates on the periphery, nucleates the formation of heterotypic TDP-43PrLD amyloid fibrils with structures distinct from those derived from homogenous solutions. Together, these results reveal an intriguing property of αS as a Pickering agent in interacting with SGs and unmask the hitherto unknown role of αS in modulating TDP-43 proteinopathies.
Gut microbiome remains stable following COVID-19 vaccination in healthy and immuno-compromised individuals
Authors: Boston Rebecca H. , Guan Rui , Kalmar Lajos , Beier Sina , Horner Emily C. , Beristain-Covarrubias Nonantzin , Yam-Puc Juan Carlos , Gerber Pehuén Pereyra , Faria Luisa , Kuroshchenkova Anna , Lindell Anna E. , Blasche Sonja , Correa-Noguera Andrea , Elmer Anne , Saunders Caroline , Bermperi Areti , Jose Sherly , Kingston Nathalie ,   CITIID-NIHR COVID-19 BioResource Collaboration, Grigoriadou Sofia , Staples Emily , Buckland Matthew S. , Lear Sara , Matheson Nicholas J. , Benes Vladimir , Parkinson Christine , Thaventhiran James E. D. , Patil Kiran R.
Published: August 2023

The bidirectional interaction between the immune system and the gut microbiota is a key contributor to various host physiological functions. Immune-associated diseases such as cancer and autoimmunity, as well as the efficacy of immunomodulatory therapies, have been linked to microbiome variation. While COVID-19 infection has been shown to cause microbial dysbiosis, it remains understudied whether the inflammatory response associated with vaccination also impacts the microbiota. Here, we investigate the temporal impact of COVID-19 vaccination on the gut microbiome in healthy and immuno-compromised individuals; the latter included patients with primary immunodeficiency and cancer patients on immunomodulating therapies. We find that the gut microbiome remained remarkably stable post-vaccination irrespective of diverse immune status, vaccine response, and microbial composition spanned by the cohort. The stability is evident at all evaluated levels including diversity, phylum, species, and functional capacity. Our results indicate the resilience of the gut microbiome to host immune changes triggered by COVID-19 vaccination and suggest minimal, if any, impact on microbiome-mediated processes. These findings encourage vaccine acceptance, particularly when contrasted with the significant microbiome shifts observed during COVID-19 infection.
Designing Efficient Enzymes: Eight Predicted Mutations Convert a Hydroxynitrile Lyase into an Efficient Esterase
Authors: Casadevall Guillem , Pierce Colin , Guan Bo , Iglesias-Fernandez Javier , Lim Huey-Yee , Greenberg Lauren R. , Walsh Meghan E. , Shi Ke , Gordon Wendy , Aihara Hideki , Evans Robert L. , Kazlauskas Romas , Osuna Sílvia
Published: August 2023

Hydroxynitrile lyase from rubber tree (HbHNL) shares 45% identical amino acid residues with the homologous esterase from tobacco, SABP2, but the two enzymes catalyze different reactions. The x-ray structures reveal a serine-histidine-aspartate catalytic triad in both enzymes along with several differing amino acid residues within the active site. Previous exchange of three amino acid residues in the active site ofHbHNL with the corresponding amino acid residue in SABP2 (T11G-E79H-K236M) created variant HNL3, which showed low esterase activity toward p-nitrophenyl acetate. Further structure comparison reveals additional differences surrounding the active site.HbHNL contains an improperly positioned oxyanion hole residue and differing solvation of the catalytic aspartate. We hypothesized that correcting these structural differences would impart good esterase activity on the corresponding HbHNL variant. To predict the amino acid substitutions needed to correct the structure, we calculated shortest path maps for bothHbHNL and SABP2, which reveal correlated movements of amino acids in the two enzymes. Replacing four amino acid residues (C81L-N104T-V106F-G176S) whose movements are connected to the movements of the catalytic residues yielded variant HNL7TV (stabilizing substitution H103V was also added), which showed an esterase catalytic efficiency comparable to that of SABP2. The x-ray structure of an intermediate variant, HNL6V, showed an altered solvation of the catalytic aspartate and a partially corrected oxyanion hole. This dramatic increase in catalytic efficiency demonstrates the ability of shortest path maps to predict which residues outside the active site contribute to catalytic activity.
Lignin impairs Cel7A degradation of cellulose by impeding enzyme movement and not by acting as a sink
Authors: Haviland Zachary K. , Nong Daguan , Zexer Nerya , Tien Ming , Anderson Charles T. , Hancock William O.
Published: August 2023

Background

Cellulose degradation by cellulases has been studied for decades due to the potential of using lignocellulosic biomass as a sustainable source of bioethanol. In plant cell walls, cellulose is bonded together and strengthened by the polyphenolic polymer, lignin. Because lignin is tightly linked to cellulose and is not digestible by cellulases, is thought to play a dominant role in limiting the efficient enzymatic degradation of plant biomass. Removal of lignin via pretreatments currently limits the cost-efficient production of ethanol from cellulose, motivating the need for a better understanding of how lignin inhibits cellulase-catalyzed degradation of lignocellulose. Work to date using bulk assays has suggested three possible inhibition mechanisms: lignin blocks access of the enzyme to cellulose, lignin impedes progress of the enzyme along cellulose, or lignin binds cellulases directly and acts as a sink.

Results

We used single-molecule fluorescence microscopy to investigate the nanoscale dynamics of Cel7A fromTrichoderma reesei, as it binds to and moves along purified bacterial cellulose in vitro. Lignified cellulose was generated by polymerizing coniferyl alcohol onto purified bacterial cellulose, and the degree of lignin incorporation into the cellulose meshwork was analyzed by optical and electron microscopy. We found that Cel7A preferentially bound to regions of cellulose where lignin was absent, and that in regions of high lignin density, Cel7A binding was inhibited. With increasing degrees of lignification, there was a decrease in the fraction of Cel7A that moved along cellulose rather than statically binding. Furthermore, with increasing lignification, the velocity of processive Cel7A movement decreased, as did the distance that individual Cel7A molecules moved during processive runs.

Conclusions

In an in vitro system that mimics lignified cellulose in plant cell walls, lignin did not act as a sink to sequester Cel7A and prevent it from interacting with cellulose. Instead, lignin both blocked access of Cel7A to cellulose and impeded the processive movement of Cel7A along cellulose. This work implies that strategies for improving biofuel production efficiency should target weakening interactions between lignin and cellulose surface, and further suggest that nonspecific adsorption of Cel7A to lignin is likely not a dominant mechanism of inhibition.
Ferredoxin 1 is essential for embryonic development and lipid homeostasis
Authors: Mohibi Shakur , Zhang Yanhong , Perng Vivian , Chen Mingyi , Zhang Jin , Chen Xinbin
Published: August 2023

Mammalian ferredoxin 1 and 2 (FDX1/2) belong to an evolutionary conserved family of iron-sulfur cluster containing proteins and act as electron shutters between ferredoxin reductase (FDXR) and numerous proteins involved in critical biological pathways. FDX1 is involved in biogenesis of steroids and bile acids, Vitamin A/D metabolism, and lipoylation of tricarboxylic acid (TCA) cycle enzymes. FDX1 has been extensively characterized biochemically but its role in physiology and lipid metabolism has not been explored. In this study, we generatedFdx1-deficient mice and showed that knockout of both alleles of theFdx1gene led to embryonic lethality. We also showed that likeFdxr+/−mice,Fdx1+/−mice had a shorter life span and were prone to steatohepatitis. However, unlikeFdxr+/−mice,Fdx1+/−mice were not prone to spontaneous tumors. Additionally, we showed that FDX1 deficiency led to lipid droplet accumulation possibly via the ABCA1-SREBP1/2 pathway. Specifically, untargeted lipidomic analysis showed that FDX1 deficiency led to alterations in several classes of lipids, including cholesterol, triacylglycerides, acylcarnitines, ceramides, phospholipids and lysophospholipids. Taken together, our data indicate that FDX1 is essential for mammalian embryonic development and lipid homeostasis at both cellular and organismal levels.