bluuebunny/crossref_metadata_2025 huggingface dataset:
Nasal Spray of Neutralizing Monoclonal Antibody 35B5 Confers Potential Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern: A Small-Scale Clinical Trial
Authors: Lin Yao , Yue Shuai , Yang Yang , Yang Sen , Pan Zhiwei , Yang Xiaofan , Gao Leiqiong , Zhou Jing , Li Zhirong , Hu Li , Tang Jianfang , Wu Qing , Lei Shun , Tian Qin , Wang Yifei , Hao Yaxing , Xu Lifan , Huang Qizhao , Zhu Bo , Chen Yaokai , Chen Xiangyu , Ye Lilin
Published: June 2022

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), especially the Delta and Omicron variants, have been reported to show significant resistance to approved neutralizing monoclonal antibodies (mAbs) and vaccines. We previously identified a mAb named 35B5 that harbors broad neutralization to SARS-CoV-2 VOCs. Herein, we explored the protection efficacy of a 35B5-based nasal spray against SARS-CoV-2 VOCs in a small-scale clinical trial.

Methods

We enrolled 30 healthy volunteers who were nasally administered the modified 35B5 formulation. At 12, 24, 48, and 72 hours after nasal spray, the neutralization efficacy of nasal mucosal samples was assayed with pseudoviruses coated with SARS-CoV-2 spike protein of the wild-type strain or the Alpha, Beta, Delta, or Omicron variants.

Results

The nasal mucosal samples collected within 24 hours after nasal spray effectively neutralized SARS-CoV-2 VOCs (including Delta and Omicron). Meanwhile, the protection efficacy was 60% effective and 20% effective at 48 and 72 hours after nasal spray, respectively.

Conclusions

A single nasal spray of 35B5 formation conveys 24-hour effective protection against SARS-CoV-2 VOCs, including the Alpha, Beta, Delta, or Omicron variants. Thus, 35B5 nasal spray might be potential in strengthening SARS-CoV-2 prevention, especially in high-risk populations.

Clinical Trials Registration

2022-005-02-KY.
Contribution of Reinfection to Annual Rate of Tuberculosis Infection (ARI) and Incidence of Tuberculosis Disease
Authors: Horsburgh C Robert , Jo Youngji , Nichols Brooke , Jenkins Helen E , Russell Colin A , White Laura F
Published: June 2022

Background

Modeling studies have concluded that 60–80% of tuberculosis (TB) infections result from reinfection of previously infected persons. The annual rate of infection (ARI), a standard measure of the risk of TB infection in a community, may not accurately reflect the true risk of infection among previously infected persons. We constructed a model of infection and reinfection with Mycobacterium tuberculosis to explore the predictive accuracy of ARI and its effect on disease incidence.

Methods

We created a deterministic simulation of the progression from TB infection to disease and simulated the prevalence of TB infection at the beginning and end of a theoretical year of infection. We considered 10 disease prevalence scenarios ranging from 100/100 000 to 1000/100 000 in simulations where TB exposure probability was homogeneous across the whole simulated population or heterogeneously stratified into high-risk and low-risk groups. ARI values, rates of progression from infection to disease, and the effect of multiple reinfections were obtained from published studies.

Results

With homogeneous exposure risk, observed ARI values produced expected numbers of infections. However, when heterogeneous risk was introduced, observed ARI was seen to underestimate true ARI by 25–58%. Of the cases of TB disease that occurred, 36% were among previously infected persons when prevalence was 100/100 000, increasing to 79% of cases when prevalence was 1000/100 000.

Conclusions

Measured ARI underestimates true ARI as a result of heterogeneous population mixing. The true force of infection in a community may be greater than previously appreciated. Hyperendemic communities likely contribute disproportionally to the global TB disease burden.
A Descriptive Qualitative Study of Foreign Caregivers of Older Adult Stroke Survivors
Authors: Septi Mauludina Yosika , Yeni Kustanti Christina , Fields Beth E , Chang Feng-Hang
Published: June 2022

Background and Objectives

With a growing aging stroke population and the changing structure of the society, the demand for foreign caregivers has rapidly increased in Taiwan and many other developed countries. However, little is known regarding the perception, values, and abilities of foreign caregivers and how those may influence their quality of care. This study aimed to explore and describe the experiences of Indonesian foreign caregivers, the largest migrant working population in Taiwan, who reside with and provide support to older adults with stroke and their families.

Research Design and Methods

By adopting a descriptive qualitative approach, we conducted semistructured interviews with 22 Indonesian caregivers (mean age: 36 years) who were providing care to community-dwelling older stroke survivors (age ≥ 65 years) in Taiwan. Data were analyzed through thematic analysis.

Results

Six themes were constructed from the interviews: (a) foreign caregiver’s background, (b) foreign caregiver’s perception of the health and functional status of stroke survivors, (c) foreign caregiver’s values and preferences, (d) consequences of caring for stroke survivors, (e) skills/abilities/knowledge of foreign caregivers to provide stroke survivors with required care, and (f) potential resources that foreign caregivers can use.

Discussion and Implications

Foreign caregivers described the positive and negative aspects of caring for stroke survivors. Differences in language, religion, culture, values, and expectations between foreign caregivers and stroke survivors influence the caregiving experience. These findings can help Taiwan and other developed countries to better support foreign caregivers providing critical care to older adults with stroke and their families.
The Costs and Benefits of Environmental Memory for Reef-Building Corals Coping with Recurring Marine Heatwaves
Authors: Brown Kristen T , Barott Katie L
Published: June 2022

Marine heatwaves are occurring more frequently as climate change intensifies, resulting in global mass coral bleaching events several times per decade. Despite the time between marine heatwaves decreasing, there is evidence that reef-building corals can develop increased bleaching resistance across repetitive marine heatwaves. This phenomenon of acclimatization via environmental memory may be an important strategy to ensure coral persistence; however, we still understand very little about the apparent acclimatization or, conversely, sensitization (i.e., stress accumulation or weakening) of reef-building corals to consecutive heatwaves and its implications for the trajectory and resilience of coral reefs. Here, we highlight that not only will some corals become stress hardened via marine heatwaves, but many other individuals will suffer sensitization during repeat heatwaves that further exacerbates their stress response during repeat events and depresses fitness. Under current and predicted climate change, it is necessary to gain a better understanding of the acclimatization vs. sensitization trajectories of different species and individuals on the reef, as well as identify whether changes in bleaching susceptibility relates to physiological acclimatization, trade-offs with other biological processes, and ultimately coral persistence in the Anthropocene.
TECHNICAL NOTE: Analysis of volatile fatty acids in rumen fluid by gas chromatography mass spectrometry using a dimethyl carbonate extraction
Authors: Foote Andrew P
Published: June 2022

Analysis of rumen fluid volatile fatty acids (VFA) is typically conducted by injecting acidified aqueous rumen fluid into a gas chromatograph (GC) with a flame ionization detector (FID). Aqueous samples are highly problematic because of the large vapor volume that can lead to poor peak shape and contamination of inlets, potentially causing sample carryover. Methods using aqueous samples are not well suited for use in a mass spectrometer (MS) detector system. The objective of this project was to validate a dimethyl carbonate (DMC) extraction process and GCMS method for rumen VFA analysis. To perform the extraction, 100 µL of sample, KHSO4 (500 g/L), and 2-ethylbutyrate (internal standard; 8.5 mM) were added to a microcentrifuge tube (in order) followed by 1 mL of DMC. The mixture was thoroughly vortexed and centrifuged. The organic layer (top) was removed and placed in a GC vial. The DMC extract was injected (0.5 µL) into an Agilent 5977B GCMS (8:1 split injection) with a polar DB-FFAP column. The column was held at 105 °C for 5 min, increased at 10 °C/min to 150 °C, then 65 °C/min to 240 °C, and held constant for 10 min. The peak area of acetate relative to the internal standard is linear from approximately 2 mM to at least 130 mM and encompasses the expected values of rumen concentrations for the other VFA. Recovery of VFA from spiked rumen fluid was tested at three concentrations in rumen fluid from steers fed a finishing diet or grazing wheat pasture. Recovery was not affected by the diet of the animals (P > 0.10) or the amount of VFA spiked (P > 0.19) for acetate, propionate, isobutyrate, or butyrate. There was an interaction of amount of VFA spiked and the diet of the animal (P = 0.021) for valerate and a tendency for an interaction (P = 0.051) for isovalerate, due to the recovery of the VFA being lower in the medium spike amount in rumen fluid from cattle on wheat pasture. Overall, recovery was greatest for propionate (101.9 ± 1.67%) and lowest for valerate (95.7 ± 1.95%). Including the 10-min hold at 240 °C at the end of each run prevented carryover from sample to sample. This method appears to perform well in a GCMS system and accurately and precisely quantifies rumen fluid VFA.
Patient Sociodemographic Characteristics Associated With Saturday Breast Imaging Clinic Utilization
Authors: Miles Randy C , Lehman Constance D , Chou Shinn-Huey S , Sohn Young-Jin , Guerrier Claude E , Wang Gary X , Narayan Anand K
Published: June 2022

Objective

To determine patient sociodemographic characteristics associated with breast imaging utilization on Saturdays to inform potential initiatives designed to improve access and reduce disparities in breast cancer care.

Methods

This was an IRB-approved retrospective cross-sectional study. All adult women (aged ≥18 years) who received a screening or diagnostic examination at our breast imaging facility from January 1, 2016 to December 31, 2017 were included. Patient characteristics including age, race, primary language, partnership status, insurance status, and primary care physician status were collected using the electronic medical record. Multiple variable logistic regression analyses were performed to evaluate patient characteristics associated with utilization.

Results

Of 53 695 patients who underwent a screening examination and 10 363 patients who underwent a diagnostic examination over our study period, 9.6% (5135/53 695) and 2.0% (209/10 363) of patients obtained their respective examination on a Saturday. In our multiple variable logistic regression analyses, racial/ethnic minorities (odds ratio [OR], 1.5; 95% confidence interval [CI]: 1.4–1.6; P < 0.01) and women who speak English as a second language (OR, 1.1; 95% CI: 1.0–1.3; P = 0.03) were more likely to obtain their screening mammogram on Saturday than their respective counterparts.

Conclusion

Racial/ethnic minorities and women who speak English as a second language were more likely to obtain their screening mammogram on Saturdays than their respective counterparts. Initiatives to extend availability of breast imaging exams outside of standard business hours increases access for historically underserved groups, which can be used as a tool to reduce breast cancer–related disparities in care.
Biofilm and hyphal inhibitory synergistic effects of phytoactives piperine and cinnamaldehyde against Candida albicans
Authors: Priya Arumugam , Pandian Shunmugiah Karutha
Published: June 2022

Oral candidiasis, the most common mycotic infection of the human oral cavity is non-life-threatening yet, if untreated, may advance as systemic infections. The ability of Candida albicans to adapt sessile lifestyle imparts resistance to drugs and host immunity. Consequently, due to the limited effectiveness of conventional antifungal treatment, novel therapeutic strategies are required. In the present study, synergistic interaction of phytochemicals, piperine, and cinnamaldehyde against the biofilm and hyphal of C. albicans was evaluated. Minimum inhibitory concentration (MIC) and biofilm inhibitory concentration (BIC) of piperine and cinnamaldehyde against C. albicans were analyzed through microbroth dilution assay and crystal violet staining method, respectively. Combinatorial biofilm and hyphal inhibitory effect were investigated through checkerboard assay. In vitro results were validated through gene expression analysis. BIC of piperine and cinnamaldehyde was determined to be 32 μg/ml and 64 μg/ml, respectively. Interaction between these two phytocomponents was found to be synergistic and six different synergistic antibiofilm combinations were identified. Microscopic analysis of biofilm architecture also evidenced the biofilm and surface adherence inhibitory potential of piperine and cinnamaldehyde combinations. Phenotypic switching between yeast and hyphal morphological forms was influenced by synergistic combinations. qPCR analysis corroborated the results of in vitro activities. nrg1 and trp1, the negative transcriptional regulators of filamentous growth were upregulated whereas other genes that are involved in biofilm formation, filamentous growth, adhesion, etc. were found to be downregulated. These proficient phytochemical combinations provide a new therapeutic avenue for the treatment of biofilm-associated oral candidiasis and to combat the recurrent infections due to antibiotic resistance.

Lay abstract
VUV photopolymerization of ketene under interstellar conditions: from the dilute phase to the condensed phase
Authors: Ibrahim Mohamad , Guillemin Jean-Claude , Krim Lahouari
Published: June 2022

The photodecomposition of ketene under interstellar conditions and how the resulting photofragments may recombine in the 3–300 K temperature range could play an important role in investigations related to astrochemistry and astrobiology. Using a combination of bulk ice and rare-gas matrix isolation studies coupled to Fourier transform infrared (FTIR) spectroscopy, this work aims to understand the vacuum ultraviolet (VUV) photochemistry of CH2CO in solid phase to mimic the photochemistry of organic species trapped in the icy interstellar grains. We show that the photolysis of CH2CO depends strongly on the environments where it is trapped. The VUV photolysis of CH2CO/Ne in dilute phase leads to kinetically stable and unstable species such as CO, C2H2, CH4, C2H4, C2H6, H2CO, CH3CHO, HCCO, C2O, C3O, and C4O. However, the same experiment carried out in condensed phase shows that the photolysis of CH2CO ice produces mainly an organic residue, which is directly observed at 10 K and remains stable in solid phase at 300 K. The infrared (IR) spectroscopy analysis suggests that the resulting organic residue could be a polyketone formed at 10 K through the VUV photopolymerization of ketene.
A case of aortoduodenal fistula caused by IgG4-related periaortitis
Authors: Oka Hideki , Sumitomo Shuji , Shimizu Hayato , Kanamori Maki , Yamashita Daisuke , Nishioka Hiroaki , Ohmura Koichiro
Published: June 2022

An 86-year-old man who underwent endovascular aortic repair for impending rupture of an abdominal aortic aneurysm a year ago presented to our hospital because of fatigue and black stools. Multiple bacterial specimens were detected in blood cultures, and computed tomography following oral administration of gastrografin demonstrated gastrografin in the abdominal aorta. The diagnosis of aortic duodenal fistula was confirmed and emergency abdominal aortic replacement was performed. The pathological findings of the aorta included a large number of immunoglobulin G4 (IgG4)-positive plasma cells infiltrating all layers of the aortic wall, with particularly marked thickening of the adventitia. The serum IgG4 level was 241 mg/dl and IgG4-related periaortitis was diagnosed. Aortoduodenal fistula is a rare but fatal complication of IgG4-related periaortitis. Patients should be followed carefully after endovascular aortic repair for inflammatory abdominal aortic aneurysms.
Epigenetic dysregulation in meningiomas
Authors: Wedemeyer Michelle A , Muskens Ivo , Strickland Ben A , Aurelio Oscar , Martirosian Vahan , Wiemels Joseph L , Weisenberger Daniel J , Wang Kai , Mukerjee Debraj , Rhie Suhn K , Zada Gabriel
Published: June 2022

Background

Meningiomas are the most common primary brain tumor. Though typically benign with a low mutational burden, tumors with benign histology may behave aggressively and there are no proven chemotherapies. Although DNA methylation patterns distinguish subgroups of meningiomas and have higher predictive value for tumor behavior than histologic classification, little is known about differences in DNA methylation between meningiomas and surrounding normal dura tissue.

Methods

Whole-exome sequencing and methylation array profiling were performed on 12 dura/meningioma pairs (11 WHO grade I and 1 WHO grade II). Single-nucleotide polymorphism (SNP) genotyping and methylation array profiling were performed on an additional 19 meningiomas (9 WHO grade I, 5 WHO grade II, 4 WHO grade III).

Results

Using multimodal studies of meningioma/dura pairs, we identified 4 distinct DNA methylation patterns. Diffuse DNA hypomethylation of malignant meningiomas readily facilitated their identification from lower-grade tumors by unsupervised clustering. All clusters and 12/12 meningioma-dura pairs exhibited hypomethylation of the gene promoters of a module associated with the craniofacial patterning transcription factor FOXC1 and its upstream lncRNA FOXCUT. Furthermore, we identified an epigenetic continuum of increasing hypermethylation of polycomb repressive complex target promoters with increasing histopathologic grade.

Conclusion

These findings support future investigations of the role of epigenetic dysregulation of FOXC1 and cranial patterning genes in meningioma formation as well as studies of the utility of polycomb inhibitors for the treatment of malignant meningiomas.
Leptospirosis in Retirees Living in Rural Areas: A Poorly Recognized Emerging Problem in Mainland France?
Authors: Vibert Mathilde , Guimard Thomas , Brochard Julia , Takoudju Eve-Marie , Larrose Catherine , Boutoille David , Le Turnier Paul
Published: June 2022

Among 40 patients diagnosed with leptospirosis in 3 hospitals of western mainland France between 2014 and 2018, half were at least 60 years old and retired. Their exposure factors were mainly rural residential environment with limited remarkable risk factors. Better awareness and information on leptospirosis appear necessary in this population.
Leaf cell-specific and single-cell transcriptional profiling reveals a role for the palisade layer in UV light protection
Authors: Procko Carl , Lee Travis , Borsuk Aleca , Bargmann Bastiaan O R , Dabi Tsegaye , Nery Joseph R , Estelle Mark , Baird Lisa , O’Connor Carolyn , Brodersen Craig , Ecker Joseph R , Chory Joanne
Published: June 2022

Like other complex multicellular organisms, plants are composed of different cell types with specialized shapes and functions. For example, most laminar leaves consist of multiple photosynthetic cell types. These cell types include the palisade mesophyll, which typically forms one or more cell layers on the adaxial side of the leaf. Despite their importance for photosynthesis, we know little about how palisade cells differ at the molecular level from other photosynthetic cell types. To this end, we have used a combination of cell-specific profiling using fluorescence-activated cell sorting and single-cell RNA-sequencing methods to generate a transcriptional blueprint of the palisade mesophyll in Arabidopsis thaliana leaves. We find that despite their unique morphology, palisade cells are otherwise transcriptionally similar to other photosynthetic cell types. Nevertheless, we show that some genes in the phenylpropanoid biosynthesis pathway have both palisade-enriched expression and are light-regulated. Phenylpropanoid gene activity in the palisade was required for production of the ultraviolet (UV)-B protectant sinapoylmalate, which may protect the palisade and/or other leaf cells against damaging UV light. These findings improve our understanding of how different photosynthetic cell types in the leaf can function uniquely to optimize leaf performance, despite their transcriptional similarities.
Controllable synthesis of layered black bismuth oxidechloride nanosheets and their applications in internal tumor ablation
Authors: Fang Qianlan , Xu Yu , Luo Lijia , Liu Chuang , Li Zihou , Lin Jie , Chen Tianxiang , Wu Aiguo
Published: June 2022

The recently emerging bismuth oxyhalide (BiOX) nanomaterials are promising indirect band gap photosensitizer for ultraviolet (UV) light-triggered phototherapy due to their unique layered nanosheet structure. However, the low absorption and poor photothermal conversion efficiency have always impeded their further applications in cancer clinical therapy. Herein, BiOCl rich in oxygen vacancies has been reported to have full-spectrum absorption properties, making it possible to achieve photothermal property under near-infrared laser. Under 808 nm irradiation, the photothermal conversion efficiency of black BiOCl nanosheets (BBNs) is up to 40%. BBNs@PEG can effectively clear primary subcutaneous tumors and prevent recurrence, achieving good synergistic treatment effect. These results not only broke the limitation of UV on the BiOCl material and provided a good template for other semiconductor materials, but also represent a promising approach to fabricate BBN@PEG a novel, potent and multifunctional theranostic platform for precise photothermal therapy and prognostic evaluation.
Three-dimensional bioprinting sodium alginate/gelatin scaffold combined with neural stem cells and oligodendrocytes markedly promoting nerve regeneration after spinal cord injury
Authors: Liu Shuo , Yang Hui , Chen Dong , Xie Yuanyuan , Tai ChenXu , Wang Liudi , Wang Peng , Wang Bin
Published: June 2022

Accumulating research has indicated that the transplantation of combined stem cells and scaffolds is an effective method for spinal cord injury (SCI). The development of three-dimensional (3D) bioprinting technology can make the 3D scaffolds combined with cells more accurate and effective for SCI treatment. However, unmyelinated newborn nerve fibers have no nerve signaling conduction, hampering recovery of motor function. In this study, we designed and printed a type of sodium alginate/gelatin scaffold loaded with neural stem cells and oligodendrocytes, which were involved in the formation of the myelin sheaths of neural cell axons. In order to observe the effectiveness of this 3D bioprinting scaffold, we transplanted it into the completely transected rat spinal cord, and then immunofluorescence staining, hematoxylin–eosin staining and behavioral assessment were performed. The results showed that this 3D bioprinting scaffold markedly improved the hindlimb motor function and promoted nerve regeneration. These findings suggested that this novel 3D bioprinting scaffold was a good carrier for cells transplantation, thereby enhancing spinal cord repair following injury.
The Value of Differing Points of View: Evidence from Financial Analysts’ Geographic Diversity
Authors: Gerken William C , Painter Marcus O
Published: June 2022

Using satellite imagery of retail firms’ parking lots to measure time-varying local firm-specific performance, we document that analysts incorporate local information into their forecasts. Analysts rely more on local signals when less firm-wide information is available. This incorporation of noisy local firm information has firm-level implications. Examining across industries, we find causal evidence that geographic concentration of analysts increases consensus forecast errors and decreases firm liquidity. These effects are stronger for harder-to-value stocks. The market values geographic firm information, as the abnormal return around forecast revisions is higher for analysts who cover a firm from a unique location.
Gestational Age-Specific Nomogram of Transcutaneous Bilirubin in First 120 h of Life for Term and Late Preterm Indian Neonates
Authors: Shaw Subhash Chandra , Negi Vandana , Bhat Vivek , Kumar Ashutosh , Joshi Rajneesh K , Venkatnarayan Kannan , Gupta Rakesh , Kunwar Bishwo Raj Bdr , Gopalakrishnan Shridhar , Tewari Vishal Vishnu , Kanitkar Madhuri
Published: June 2022

Objective

To create a nomogram based on transcutaneous bilirubin values (TCB) in first week of life for term and late preterm (>34 weeks) neonates.

Methods and design

Prospective longitudinal study.

Setting

Four tertiary-care teaching hospitals (one each in eastern and southern India, two in northern India) between February 2019 and March 2020.

Participants

A total of 2492 term and late preterm (>34 weeks) neonates.

Intervention

Bilirubin was measured by transcutaneous bilirubinometer (Drager JM-105, Germany) in all neonates in pre-specified times of the day, 12 hourly every day since birth till discharge between 48 and 72 h, and data were recorded in epochs of 6 hourly intervals. Post-discharge, all neonates were called for review in next 48 h.

Outcome measures

Primary—TCB in first week of life. Secondary—factors having significant association with significant hyperbilirubinaemia requiring phototherapy.

Results

Total of 2492 neonates (males 1303 and female 1189), with a total of 14 162 TCB recordings were analysed and mean hourly bilirubin (TCB) at hourly intervals till 120 h and then daily bilirubin values on Days 6 and 7 were tabulated. We have constructed hour-specific bilirubin nomogram with percentiles as per gestational age in term and near-term Indian neonates till 120 h of life. Amongst the known risk factors, delayed cord clamping, primipara and breastfeeding jaundice had significant association for hyperbilirubinaemia needing phototherapy.

Conclusions

We have created gestation-specific nomogram of TCB levels in 6 hourly intervals for the first 120 postnatal hours, obtained from a large predominantly breast fed healthy, term and near-term Indian neonates.
Emerging approaches in the diagnosis and therapy in shellfish allergy
Authors: Wai Christine Y.Y. , Leung Patrick S.C.
Published: June 2022

Purpose of review

Despite the high prevalence of shellfish allergy, the clinical management of seafood allergy has remained unchanged over decades. Here, we examined the current status in the diagnosis and clinical management of shellfish allergy and highlighted the imminent need for more specific diagnostic methods, as well as effective and safe therapeutic approaches for shellfish allergy.

Recent findings

With the advancement in the molecular identifications and definition of reactive epitopes of shellfish allergens, new diagnostic designs such as component-resolved diagnosis, basophil activation test (BAT) and the emerging IgE-crosslinking-induced luciferase expression are emerging. Furthermore, various allergen-specific immunotherapy strategies (such as shellfish extracts and allergens, hypoallergens, hypoallergen DNA vaccines, mimotopes and peptide-based therapies) are being explored at preclinical stages whereas limited nonallergen specific immunotherapy approaches are under clinical trials.

With an increasing understanding of the underlying immunological mechanisms and molecular features of shellfish allergy, the future for developing precise diagnostic and therapeutic strategies to better manage shellfish allergy is promising.
Identifying Mental Health Needs in the Faith Community
Authors: Gallo Veronica
Published: June 2022

Nearly one in five Americans suffers from a mental health disorder, and mental health issues have escalated during the COVID-19 pandemic. As trusted members of the community, faith community nurses are in a key position to assess mental health needs and take leadership roles in the faith community to address these needs. The aim of this project was to assess the mental health needs of one faith community. Qualitative data with quantitative data from secondary sources were gathered. Analysis revealed three problems for those suffering from mental health disorders: lack of resilience and coping strategies, fear and/or ignorance of mental health disorders, and unfamiliarity with community and health resources.
Cultivating Students' Practice of Prayer with Patients
Authors: Keesee Lea , Nease Sandy , Gallegos Belinda
Published: June 2022

Educating prelicensure nurses about the positive outcomes of prayer can improve the potential for nurses to develop their skill and readiness to pray with or for patients as is appropriate and ethical. When nursing students learn to pray with their patients and families, the trusting component of the nurse-patient relationship becomes strengthened. As faculty and preceptors role-model praying with patients, students can begin to develop competency in providing spiritual care.
Internet of Things for beyond-the-laboratory prosthetics research
Authors: Wu Hancong , Dyson Matthew , Nazarpour Kianoush
Published: June 2022

Research on upper-limb prostheses is typically laboratory-based. Evidence indicates that research has not yet led to prostheses that meet user needs. Inefficient communication loops between users, clinicians and manufacturers limit the amount of quantitative and qualitative data that researchers can use in refining their innovations. This paper offers a first demonstration of an alternative paradigm by which remote, beyond-the-laboratory prosthesis research according to user needs is feasible. Specifically, the proposed Internet of Things setting allows remote data collection, real-time visualization and prosthesis reprogramming through Wi-Fi and a commercial cloud portal. Via a dashboard, the user can adjust the configuration of the device and append contextual information to the prosthetic data. We evaluated this demonstrator in real-time experiments with three able-bodied participants. Results promise the potential of contextual data collection and system update through the internet, which may provide real-life data for algorithm training and reduce the complexity of send-home trials.

This article is part of the theme issue ‘Advanced neurotechnologies: translating innovation for health and well-being’.
Neural microprobe modelling and microfabrication for improved implantation and mechanical failure mitigation
Authors: McGlynn Eve , Walton Finlay , Das Rupam , Heidari Hadi
Published: June 2022

Careful design and material selection are the most beneficial strategies to ensure successful implantation and mitigate the failure of a neural probe in the long term. In order to realize a fully flexible implantable system, the probe should be easily manipulated by neuroscientists, with the potential to bend up to 90°. This paper investigates the impact of material choice, probe geometry, and crucially, implantation angle on implantation success through finite-element method simulations in
COMSOL Multiphysics
followed by cleanroom microfabrication. The designs introduced in this paper were fabricated using two polyimides: (i) PI-2545 as a release layer and (ii) photodefinable HD-4110 as the probe substrate. Four different designs were microfabricated, and the implantation tests were compared between an agarose brain phantom and lamb brain samples. The probes were scanned in a 7 T PharmaScan MRI coil to investigate potential artefacts. From the simulation, a triangular base and 50 µm polymer thickness were identified as the optimum design, which produced a probe 57.7 µm thick when fabricated. The probes exhibit excellent flexibility, exemplified in three-point bending tests performed with a DAGE 4000Plus. Successful implantation is possible for a range of angles between 30° and 90°.

This article is part of the theme issue ‘Advanced neurotechnologies: translating innovation for health and well-being’.
Cleanroom strategies for micro- and nano-fabricating flexible implantable neural electronics
Authors: Walton Finlay , Cerezo-Sanchez Maria , McGlynn Eve , Das Rupam , Heidari Hadi
Published: June 2022

Implantable electronic neural interfaces typically take the form of probes and are made with rigid materials such as silicon and metals. These have advantages such as compatibility with integrated microchips, simple implantation and high-density nanofabrication but tend to be lacking in terms of biointegration, biocompatibility and durability due to their mechanical rigidity. This leads to damage to the device or, more importantly, the brain tissue surrounding the implant. Flexible polymer-based probes offer superior biocompatibility in terms of surface biochemistry and better matched mechanical properties. Research which aims to bring the fabrication of electronics on flexible polymer substrates to the nano-regime is remarkably sparse, despite the push for flexible consumer electronics in the last decade or so. Cleanroom-based nanofabrication techniques such as photolithography have been used as pattern transfer methods by the semiconductor industry to produce single nanometre scale devices and are now also used for making flexible circuit boards. There is still much scope for miniaturizing flexible electronics further using photolithography, bringing the possibility of nanoscale, non-invasive, high-density flexible neural interfacing. This work explores the fabrication challenges of using photolithography and complementary techniques in a cleanroom for producing flexible electronic neural probes with nanometre-scale features.

This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.
An affordable implantable vagus nerve stimulator system for use in animal research
Authors: Canal-Alonso Ángel , Casado-Vara Roberto , Castellano Orlando , Herrera-Santos Jorge , Gonçalves Jaime , Màrquez-Sànchez Sergio , Gonçalves Jesús María , Corchado Juan Manuel
Published: June 2022

In this research, a vagus nerve stimulator has been developed and miniaturized for use in epilepsy research. The board contains all the components necessary for its operation during the standard duration of the experiments, being possible to control it once implanted and even being able to reuse it. The VNS system has been designed for rodents since the VNS devices available for human are not only too large for laboratory animals, but also too expensive. With this solution the expenditure on materials made by laboratories is greatly reduced and bioethical considerations were kept in mind. The system was validated in hamsters.

This article is part of the theme issue ‘Advanced neurotechnologies: translating innovation for health and well-being’.
Multiscale simulation analysis of passive and active micro/nanoelectrodes for CMOS-based
in vitro
neural sensing devices
Authors: Leva Federico , Palestri Pierpaolo , Selmi Luca
Published: June 2022

Neuron and neural network studies are remarkably fostered by novel stimulation and recording systems, which often make use of biochips fabricated with advanced electronic technologies and, notably, micro- and nanoscale complementary metal-oxide semiconductor (CMOS). Models of the transduction mechanisms involved in the sensor and recording of the neuron activity are useful to optimize the sensing device architecture and its coupling to the readout circuits, as well as to interpret the measured data. Starting with an overview of recently published integrated active and passive micro/nanoelectrode sensing devices for
in vitro
studies fabricated with modern (CMOS-based) micro-nano technology, this paper presents a mixed-mode device-circuit numerical-analytical multiscale and multiphysics simulation methodology to describe the neuron-sensor coupling, suitable to derive useful design guidelines. A few representative structures and coupling conditions are analysed in more detail in terms of the most relevant electrical figures of merit including signal-to-noise ratio.

This article is part of the theme issue ‘Advanced neurotechnologies: translating innovation for health and well-being’.
Microvirga roseola sp. nov. and Microvirga lenta sp. nov., isolated from Taklamakan Desert soil
Authors: Du Xinran , Ran Qi , Wang Jianing , Jiang Hong , Wang Jingjing , Li Yue-zhong
Published: June 2022

Two Gram-negative, rod-shaped, non-spore-forming bacteria, designated SM9T and SM2T, were isolated from Taklamakan Desert soil samples. Phylogenetic analysis based on the 16S rRNA gene sequences showed that strains SM9T and SM2T had the highest sequence similarity to the type strains

Microvirga indica

BCRC 80972T and

Microvirga soli

NBRC 112417T with similarity values of 98.2 and 97.7 %, respectively, and

Microvirga

was among the predominant genera in the desert soil. The draft genomes of these two strains were 4.56 Mbp (SM9T) and 5.08 Mbp (SM2T) long with 65.1 mol% (SM9T) and 63.5 mol% (SM2T) G+C content. To adapt to the desert environment, these two strains possessed pathways for the synthesis of stress metabolite trehalose. The major fatty acids (>5 %) included C18 : 1 ω9c in SM2T, but C16 : 0, C18 : 0 and C19 : 0 cyclo ω8c in SM9T, while the major menaquinone was ubiquinone 10 in both strains. The major polar lipids of SM9T and SM2T were phosphatidylglycerol, phosphatidylethanolamine and phospholipid. The average nucleotide identity and digital DNA–DNA hybridization results further indicated that strains SM9T and SM2T were distinguished from phylogenetically related species and represented two novel species within the genus

Microvirga

, for which the names Microvirga roseola sp. nov. (type strain SM2T=KCTC 72792T=CGMCC 1.17776T) and Microvirga lenta sp. nov. (type strain SM9T=KCTC 82729T=CCTCC AB 2021131T) are proposed.
Canadian Healthcare Providers’ Attitudes Towards Automated Insulin Delivery Systems
Authors: Morrison Amy E , Farnsworth Kate , Witteman Holly O , Lam Anna , Senior Peter A
Published: June 2022

Introduction

We aimed to assess the current experience and attitudes towards Commercial and Do-it-yourself (DIY) automated insulin delivery (AID) systems among healthcare providers (HCP) across Canada.

Methods

A cross-sectional study was performed through electronic distribution of an anonymous survey to HCP licensed to practice in Canada looking after people with type 1 diabetes (T1D).

Results

Responses included 204 HCP across the multi-disciplinary team; dieticians (32.8%), nurses (31.9%), and endocrinologists (28.4%), looking after adults (51%) and children (23%) mainly in urban areas (85.7%). Respondents reported a median 100-500 patients with T1D per practice, with a median 6-24 current users/practice of Commercial compared to a median 1-5 current users/practice of DIY AID. The majority of HCP (72.7%) were comfortable supporting Commercial AID, whereas only 21.6% reported comfort supporting DIY AID use. A significant, although moderate correlation between HCP experience and comfort was seen; Commercial r=0.57(p<0.0001) and DIY r=0.45(p<0.0001). Respondents reported more barriers to DIY, relative to Commercial AID(p=0.001); unfamiliarity/lack of exposure and medico-legal risks were highlighted with DIY systems. Respondents suggested AID system education (both Commercial and DIY), for HCP and users, to improve HCP confidence.

Conclusions

Despite documented beneficial outcomes, AID systems are not widely used in the management of T1D in Canada. The need for both user and HCP education to improve familiarity with the systems, in addition to clarity in medico-legal guidance, have been identified as gaps, which if addressed, might enable the benefits of AID to be more widely available to people with T1D in Canada.
TDP-43 subcellular mislocalisation is correlated with loss of optineurin binding for frontotemporal dementia and amyotrophic lateral sclerosis associated TBK1 missense variants
Authors: Oyston Lisa J. , Boccanfuso Lauren M. , Fitzpatrick Lauren , Zhang Johnny , Hallupp Marianne , Kwok John B. , Dobson-Stone Carol
Published: June 2022

Background

Frontotemporal dementia (FTD) is one of the most common forms of younger-onset dementia. FTD is genetically, pathologically and clinically related to amyotrophic lateral sclerosis (ALS), a rapidly progressive neurodegenerative disorder. Mutations in TANK-binding kinase 1 (TBK1) have been identified as a rare cause of FTD and ALS. TBK1 has known roles in inflammation and autophagy and interacts with other FTD and ALS proteins such as optineurin (OPTN): however, which of its roles are important to FTD/ALS pathogenesis remains undetermined. To date, >90 TBK1 rare variants have been identified in FTD/ALS patients: >50% of these are missense variants of unknown significance (VUS).

Methods

In this study, we have used a functional assay pipeline to investigate the effect of 16 TBK1 VUS with in-silico evidence of pathogenicity, together with two known pathogenic mutations and a common benign TBK1 polymorphism. Our assay pipeline evaluated the effect of TBK1 VUS on steady-state levels of TBK1, kinase activity and binding to OPTN. We also assessed the impact of TBK1 VUS on a key neuropathological feature of FTD and ALS cases: mislocalisation of neuronal TDP-43 from the nucleus to the cytoplasm.

Results

We observed some TBK1 VUS that had similar effects to TBK1 loss-of-function mutations, demonstrating decreased kinase activity and loss of OPTN binding. Both known pathogenic mutations and several TBK1 VUS also increased the cytoplasmic/nuclear ratio of TDP-43 and this inversely correlated with their degree of OPTN binding but not with kinase activity.

Conclusions

These results suggest that loss of the direct interaction between TBK1 and OPTN is more critical to FTD and ALS pathogenesis than TBK1’s kinase activity. However, further studies are needed to elucidate exactly how loss of TBK1 binding to OPTN leads to TDP-43 pathology and ultimately neurodegeneration.
Neurotransmission-Related Gene Expression in the Frontal Pole (Brodmann Area 10) is Altered in Subjects with Bipolar Disorder and Schizophrenia
Authors: Medina Adriana M. , Hagenauer Megan Hastings , Krolewski David M. , Hughes Evan , Thew Forrester Liam Cannon , Walsh David M. , Waselus Maria , Richardson Evelyn , Turner Cortney A. , Sequeira P. Adolfo , Cartagena Preston M. , Thompson Robert C. , Vawter Marquis P. , Bunney Blynn G. , Myers Richard M. , Barchas Jack D. , Lee Francis S.Y. , Schatzberg Alan F. , Bunney William E. , Akil Huda , Watson Stanley J.
Published: June 2022

Brodmann Area 10 (BA10) is the largest cytoarchitectonic region of the human cortex, performing complex integrative functions. BA10 undergoes intensive adolescent grey matter pruning around the average age of onset for Bipolar disorder (BP) and Schizophrenia (SCHIZ), and its dysfunction is likely to underly aspects of their shared symptomology. In this study, we investigated the role of BA10 neurotransmission-related gene expression in BP and SCHIZ. We performed qPCR to measure the expression of 115 neurotransmission-related targets in control, BP, and SCHIZ post-mortem samples (n=72). We chose this method for its high sensitivity to detect low-level expression. We then bolstered our findings by performing a meta-analysis of publicly-released BA10 microarray data (n=101) and identified sources of convergence with our qPCR results. To improve interpretation, we compiled an unusually large database of clinical metadata for our samples. We used this data to explore the relationship between BA10 gene expression, therapeutics, substances of abuse, and symptom profiles, and validated these findings with publicly-available datasets. Using these convergent sources of evidence, we identified 20 neurotransmission-related genes that were differentially expressed in BP and SCHIZ in BA10. These results included a large diagnosis-related decrease in two important therapeutic targets with low-levels of expression, HTR2B and DRD4, as well as other findings related to dopaminergic, GABA-ergic and astrocytic function. We also observed that therapeutics may produce differential expression that opposes the effects of diagnosis. In contrast, substances of abuse showed similar effects on BA10 gene expression as BP and SCHIZ, potentially amplifying diagnosis-related dysregulation.
Increased aperiodic neural activity during sleep in major depressive disorder
Authors: Rosenblum Yevgenia , Bovy Leonore , Weber Frederik D. , Steiger Axel , Zeising Marcel , Dresler Martin
Published: June 2022

Background

In major depressive disorder (MDD), patients often express subjective sleep complaints while polysomnographic studies report only subtle alterations in neural oscillations. We hypothesize that the study of aperiodic electroencephalographic (EEG) dynamics, a marker of excitation-to-inhibition balance, may bring new insights into our understanding of sleep abnormalities in MDD. Specifically, we investigate aperiodic neural activity during sleep and its relationships with the time of sleep, depression severity, and responsivity to antidepressant treatment.

Methods

Polysomnography was recorded in 38 MDD patients (in unmedicated and 7d medicated states) and 38 age-matched healthy controls (N1=76). Aperiodic EEG activity was evaluated using the Irregularly Resampled Auto-Spectral Analysis with slopes’ means and intra-individual variability as outcome measures. Depression severity was assessed with the Hamilton Depression Rating Scale. We replicated the analysis using two independently collected datasets of medicated patients and controls (N2=60, N3=80).

Results

Unmedicated patients showed flatter aperiodic slopes compared to controls during N2 (p-value=0.002) and steeper slopes compared to their later medicated state (p-values<0.02) during all sleep stages. Within unmedicated patients, slopes were flatter during late compared to early N2 sleep (p-value=0.006). Late N2 slopes further correlated with depression severity after 7d of antidepressant treatment (r=-0.34, p-value=0.04). Variability of slopes was increased in both unmedicated (p-values<0.03) and medicated states (p-values <0.006) of patients’ N2, N3, and REM sleep compared to controls.

Conclusion

Flatter slopes of aperiodic EEG power with increased variability may reflect unstable, noisy neural activity due to increased excitation-to-inhibition balance, representing a new disease-relevant feature of sleep in MDD.
Quantum biological insights into CRISPR-Cas9 sgRNA efficiency from explainable-AI driven feature engineering
Authors: Noshay Jaclyn M. , Walker Tyler , Romero Jonathon , Prates Erica , Eckert Carrie , Irle Stephan , Kainer David , Jacobson Daniel A.
Published: June 2022

CRISPR-Cas9 tools have transformed genetic manipulation capabilities in the laboratory. Empirical rules-of-thumb have been established for only a narrow range of model organisms, and mechanistic underpinnings for sgRNA efficiency remain poorly understood. This work establishes a novel feature set and new public resource, produced with quantum chemical tensors, for interpreting and predicting sgRNA efficiency. Feature engineering for sgRNA efficiency is performed using an explainable-artificial intelligence model; iterative Random Forest (iRF). By encoding quantitative attributes of position-specific sequences for E. coli sgRNAs, we identify important traits for sgRNA design in bacterial species. Additionally, we show that expanding positional encoding to quantum descriptors of base-pair, dimer, trimer and tetramer sequences captures intricate interactions in local and neighboring nucleotides of the target DNA. These features highlight variation in CRISPR-Cas9 sgRNA dynamics between E. coli and H. sapien genomes. These novel encodings of sgRNAs greatly enhance our understanding of the elaborate quantum biological processes involved in CRISPR-Cas9 machinery.