bluuebunny/crossref_metadata_2025 huggingface dataset:
Seclusion, Restraint, Therapeutic Alliance, and Legal Admission Status: What Really Matters?
Authors: O’Callaghan Aoife K. , Plunkett Róisín , Kelly Brendan D.
Published: November 2022

Objective:

To determine the relationships, if any, between use of seclusion and restraint and factors such as demographic parameters, diagnosis, legal admission status (voluntary or involuntary), symptoms, cognitive function, global functioning, therapeutic alliance, attitudes toward medication, and insight, among psychiatry inpatients in Ireland.

Methods:

We used validated tools to perform detailed assessments of 107 adult psychiatry inpatients admitted to acute psychiatry units at 2 general hospitals in Dublin, Ireland over a 30-month period, between September 2017 and February 2020.

Results:

The most common diagnoses in our sample were affective disorders (46.7%), schizophrenia and related disorders (27.1%), and personality and behavioral disorders (11.2%). Over a quarter (n=29, 27.1%) of the participating patients had involuntary legal status. Of the 107 patients, 11 patients (10.3%) experienced sedation and/or physical restraint, with 9 patients (8.4%) experiencing at least 1 episode of seclusion and 10 patients (9.3%) experiencing at least 1 episode of physical restraint. On the basis of multivariable analyses, seclusion was associated with younger age and involuntary status, while physical restraint was associated with involuntary status. Each multivariable model explained just over one third of the variance in the distribution of these seclusion and restraint practices.

Conclusions:

Use of seclusion and restraint was most strongly associated with involuntary admission status and, in the case of seclusion, younger age, rather than sex, diagnosis, symptoms, cognitive function, global functioning, therapeutic alliance, attitudes toward medication, or insight. The network of interactions between involuntary status and use of seclusion and restraint merits much closer attention, especially as use of seclusion and physical restraint appears to be associated with involuntary legal status independent of level of symptoms, therapeutic alliance, or insight.
Hazards of Using Constant Observation With Suicidal Patients
Authors: Obegi Joseph H.
Published: November 2022

Constant observation is a necessary albeit controversial procedure. Although widely used in psychiatric hospitals to maintain the safety of patients experiencing acute suicidality, constant observation is associated with many medicolegal hazards. Some hazards threaten patients directly, others undermine the effectiveness of treatment, and still others challenge clinical decision-making and suicide risk assessment. Nevertheless, clinicians can take proactive steps to minimize potentially adverse effects of constant observation on patients, preserve the integrity of treatment, and limit legal exposure.
Systematic Review of Clinical Practice Guidelines for Insomnia Disorder
Authors: Seow Su Yin , Kwok Kah Foo Victor , Tay Kai Hong , Chee Weng Seng Ashwin , Rawtaer Iris , Cheng Yao , Tan Qi Xuan , Tan Shian Ming
Published: November 2022

Objective:

This systematic review assessed the quality of clinical practice guidelines (CPGs) on the treatment of insomnia disorder and their reporting of recommendations, while summarizing the evidence and providing guidance on an algorithmic approach to appropriate pharmacological treatment.

Methods:

The PubMed and EMBASE databases, guideline repositories, and specialist association websites were searched. The quality of the CPGs was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument, complemented by the AGREE-REX (Appraisal of Guidelines REsearch and Evaluation—Recommendations EXcellence). A multidisciplinary team identified the key clinical questions that a clinician would consider when taking an algorithmic approach to the use of medication for patients with insomnia disorder. By using a meta-synthesis approach, recommendations from the CPGs were characterized and summarized via a recommendation matrix.

Results:

A total of 10 records that met the inclusion criteria were included and appraised. Four CPGs were rated as high and 3 CPGs were rated as moderate in overall quality. Most of the CPGs recommended pharmacotherapy only if cognitive behavioral therapy for insomnia or other nonpharmacological interventions were unavailable, unsuccessful, or declined by patients. Recommendations on types of medicines and dose and duration of treatment varied and were nonspecific. Few of the CPGs provided recommendations on pharmacotherapy in special populations.

Conclusions:

Indications for starting medications are the only common thread in all of the reviewed CPGs. The CPGs diverged in the choice of first-line pharmacotherapy, and most of the CPGs did not provide recommendations on all subsequent clinical considerations.
Barriers to Long-acting Injectable Antipsychotic Adherence During the COVID-19 Pandemic: Observations From One Site
Authors: Forster Sarah E. , Gancz Naomi N. , Gaither Marci L. , Haas Gretchen L. , Starver Kelly D. , Steinhauer Stuart R.
Published: November 2022

Objective:

Long-acting injectable antipsychotics (LAI-As) are a crucial treatment option for individuals with serious mental illness. However, due to the necessity of in-person administration of LAI-As, pandemics pose unique challenges for continuity of care in the population prescribed these medications. This project investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic on LAI-A adherence at a Veterans Health Administration medical facility in the United States, as well as changes in LAI-A prescribing and administration practices during this period.

Methods:

Electronic health records were evaluated for 101 patients prescribed LAI-As. A subset of 13 patients also participated in an interview and rated subjective concerns about pandemic-related barriers to medication adherence.

Results:

Pandemic-related barriers to LAI-A adherence and/or changes to LAI-A medications were documented in 33% of the patients. Within-subjects comparison of an adherence metric computed from electronic health record data further suggested a somewhat higher incidence of missed or delayed LAI-A doses during the pandemic compared with before the pandemic. In contrast, only 2 of the 13 patients interviewed anticipated that pandemic-related concerns would interfere with medication adherence.

Conclusions:

The results of this study suggest that LAI-A access and adherence can be disrupted by pandemics and other public health emergencies but this finding may not generalize to other sites. As patients may not foresee the potential for disruption, psychiatric service providers may need to assist in proactively problem-solving barriers to access. Improved preparedness and additional safeguards against pandemic-related disruptions to LAI-A access and adherence may help mitigate adverse outcomes in the future. Identifying patients at elevated risk for such disruptions may help support these efforts.
Commentary: Psychiatric Symptoms Related to Somatic Illness
Authors: Garakani Amir
Published: November 2022

Although hallucinations, particularly auditory hallucinations, are most commonly associated with psychotic disorders such as schizophrenia, patients experiencing visual and even auditory hallucinations may actually have an underlying somatic illness that is causing the symptoms. This commentary discusses 2 cases of hallucinations due to nonpsychiatric causes, including a case of a semicircular canal dehiscence causing auditory hallucinations and a case of visual hallucinations in Charles Bonnet syndrome caused by hypertensive episodes. When patients with no history of psychosis present with hallucinations, it is crucial that medical providers perform a full evaluation, including an assessment of the patient’s psychiatric history. This is especially important when a patient with no history of psychosis presents later in life with hallucinations without other psychotic symptoms such as disorganization or delusions or other signs of a thought disorder, or when a patient presents with visual hallucinations without auditory hallucinations. Psychiatric consultation services can assist patients and their medical teams in arriving at the proper diagnosis.
Transition to Inpatient Telepsychiatry Services and Impact on Quality of Care
Authors: Khurana Saranya , Pertschuk Michael , Newton Kathryn , Klein David , Du Wei
Published: November 2022

Demands for telepsychiatry have increased due to the challenges of COVID-19. The global pandemic caused a significant increase in anxiety and depression and a worsening of eating disorder symptoms, while the implementation of social distancing both exacerbated these mental health issues and disrupted the in-person delivery of mental health services. Rapid adaptation of telepsychiatry in the acute inpatient setting has been reported with favorable outcomes in patient experiences. This article reports our experience with a transition to telepsychiatry services on an acute eating disorder unit and the impact on quality of care. Forty-two inpatients on an eating disorders unit completed 410 surveys evaluating their experience with telepsychiatry. Simultaneously, surveys were distributed to physicians to identify technical and connectivity issues. Our experience showed that patients on an eating disorder unit, who had an average length of stay of 22 days, were very satisfied with telepsychiatry, with few technical or safety issues.
Impact of 68Ga-FAPI-04 PET/CT on Staging and Therapeutic Management in Patients With Digestive System Tumors
Authors: Kosmala Aleksander , Serfling Sebastian E. , Schlötelburg Wiebke , Lindner Thomas , Michalski Kerstin , Schirbel Andreas , Higuchi Takahiro , Hartrampf Philipp E. , Buck Andreas K. , Weich Alexander , Werner Rudolf A.
Published: November 2022

Purpose

We aimed to determine the impact of fibroblast activation protein inhibitor (FAPI)–directed molecular imaging on staging and therapeutic management in patients affected with digestive system tumors when compared with guideline-compatible imaging (GCI).

Patients and Methods

Thirty-two patients with tumors of the digestive system were included: colon adenocarcinoma, 2/32 (6.3%); hepatocellular carcinoma (HCC), 6/32 (18.8%); pancreatic duct adenocarcinoma (PDAC), 6/32 (18.8%), and gastroenteropancreatic neuroendocrine neoplasms, 18/32 (56.3%). All patients underwent GCI and 68Ga-FAPI-04 PET/CT within median 4 days. Staging outcomes and subsequent treatment decisions were compared between GCI and 68Ga-FAPI-04 PET/CT.

Results

Compared with GCI, 68Ga-FAPI-04 PET/CT led to staging changes in 15/32 patients (46.9%). Among those, downstaging was recorded in 3/15 cases (20.0%) and upstaging in the remaining 12/15 patients (HCC, 4/12 [33.3%]; PDAC, 4/12 [33.3%]; neuroendocrine neoplasms, 3/12 [25%]; colon adenocarcinoma, 1/12 [8.3%]). Therapeutic management was impacted in 8/32 patients (25.0%), including 4 instances of major and 4 instances of minor therapeutic changes. The highest proportion of treatment modifications was observed in patients diagnosed with PDAC and HCC in 6/8 (75%).

Conclusions

In patients affected with digestive system tumors, 68Ga-FAPI-04 PET/CT resulted in staging changes in more than 46% and therapeutic modifications in 25% of the cases, in particular in patients with HCC and PDAC. In clinical routine, such findings may favor a more widespread adoption of FAP-directed imaging in those tumor types.
Treatment-resistant manic episode in a patient diagnosed with bipolar affective disorder
Authors: Papadimitriou Nikolaos , Antoniadis Diomidis , Ververi Athina
Published: November 2022

A considerable group of patients suffering from mental health disorders do not respond adequately to pharmacological treatment. For the purposes of precision and personalized medicine, pharmacogenomics has been developed as a valuable and promising tool. The technology of identifying single nucleotide polymorphisms and genotyping supplies clinicians, and therefore their patients, with the opportunity of avoiding long-lasting ‘trial and error’ periods, reducing the risk of manifesting disturbing adverse effects during treatment. Consequently, better adherence to treatment and clinical response can be achieved, contributing to personalized treatment planning, according to a person’s genetic profile and needs. In the present report, we present a case of an individual diagnosed with bipolar affective disorder type I, who showed resistance to pharmacological treatment and underwent through pharmacogenomic investigations, in order to identify the appropriate medication for the best possible clinical response.
Phylogenomic and comparative genomic studies robustly demarcate two distinct clades of Pseudomonas aeruginosa strains: proposal to transfer the strains from an outlier clade to a novel species Pseudomonas paraeruginosa sp. nov.
Authors: Rudra Bashudev , Duncan Louise , Shah Ajit J. , Shah Haroun N. , Gupta Radhey S.
Published: November 2022

The strains of

Pseudomonas aeruginosa

exhibit considerable differences in their genotypic and pathogenic properties. To clarify their evolutionary/taxonomic relationships, comprehensive phylogenomic and comparative genomic studies were conducted on the genome sequences of 212

P

.

aeruginosa

strains covering their genetic diversity. In a phylogenomic tree based on 118 conserved proteins, the analysed strains formed two distinct clades. One of these clades, Clade-1, encompassing >70 % of the strains including the type strain DSM 50071T, represents the species P. aeruginosa sensu stricto. Clade-2, referred to in earlier work as the outlier group, with NCTC 13628T as its type strain, constitutes a novel species level lineage. The average nucleotide identity, average amino acid identity and digital DNA–DNA hybridization values between the strains from Clade-1 and Clade-2 are in the range of 93.4–93.7, 95.1–95.3 and 52–53 %, respectively. The 16S rRNA gene of

P. aeruginosa

DSM 50071T also shows 98.3 % similarity to that of NCTC 13628T. These values are lower than the suggested cut-off values for species distinction, indicating that the Clade-2 strains (NCTC 13628T) constitute a new species. We also report the identification of 12 conserved signature indels in different proteins and 24 conserved signature proteins that are exclusively found in either Clade-1 or Clade-2, providing a reliable means for distinguishing these clades. Additionally, in contrast to swimming motility, twitching motility is only present in Clade-1 strains. Based on earlier work, the strains from these two clades also differ in their pathogenic mechanisms (presence/absence of Type III secretion system), production of biosurfactants, phenazines and siderophores, and several other genomic characteristics. Based on the evidence from different studies, we propose that the Clade-2 strains constitute a novel species for which the name Pseudomonas paraeruginosa is proposed. The type strain is NCTC 13628T (=PA7T=ATCC 9027T). The description of

Pseudomonas aeruginosa

is also emended to include information for different molecular markers specific for this species.
Subclinical hepatitis E virus infection in laboratory ferrets in the UK
Authors: Lean Fabian Z. X. , Leblond Anne-Laure , Byrne Alexander M. P. , Mollett Benjamin , James Joe , Watson Samantha , Hurley Shellene , Brookes Sharon M. , Weber Achim , Núñez Alejandro
Published: November 2022

Ferrets are widely used for experimental modelling of viral infections. However, background disease in ferrets could potentially confound intended experimental interpretation. Here we report the detection of a subclinical infection of ferret hepatitis E virus (FRHEV) within a colony sub-group of female laboratory ferrets that had been enrolled on an experimental viral infection study (non-hepatitis). Lymphoplasmacytic cuffing of periportal spaces was identified on histopathology but was negative for the RNA and antigens of the administered virus. Follow-up viral metagenomic analysis conducted on liver specimens revealed sequences attributed to FRHEV and these were confirmed by reverse-transcriptase polymerase chain reaction. Further genomic analysis revealed contiguous sequences spanning 79–95 % of the FRHEV genome and that the sequences were closely related to those reported previously in Europe. Using in situ hybridization by RNAScope, we confirmed the presence of HEV-specific RNA in hepatocytes. The HEV open reading frame 2 (ORF2) protein was also detected by immunohistochemistry in the hepatocytes and the biliary canaliculi. In conclusion, the results of our study provide evidence of background infection with FRHEV in laboratory ferrets. As this infection can be subclinical, we recommend routine monitoring of ferret populations using virological and liver function tests to avoid incorrect causal attribution of any liver disease detected in in vivo studies.
Quality characteristics and antioxidant activity of traditional
Korean soy sauce based on the proportion of onion juice
Authors: Lee Chae-Mi , Kim Su-Hwan , Jeong Jae-Hee , Choi Yu-Ri , Lee Dong-Hun , Lee Chae-Yun , Choi Byung-Kuk , Huh Chang-Ki
Published: November 2022

The aim of this study was to improve the quality and functionality of Korean soy
sauce made with onion juice. At the end of fermentation, the titratable acidity
of the soy sauce containing 100% onion juice was the highest at 2.90%. The salt
(NaCl) content was highest and lowest in the samples without and with onion
juice supplementation, respectively. The protein content ranged from
11.09-12.50%. The sensory evaluation revealed that the soy sauce sample
containing 70% onion juice had the highest scove at 5.0-5.8 levels in terms of
sweetness, salty taste, delicate flavor, and overall preference. Quercetin
content was 1.73 mg/100 g and 1.68 mg/100 g in soy sauce containing 70% and 100%
onion juice, respectively. However, quercetin was not detected in the soy sauce
without onion juice supplementation. Total polyphenol and flavonoid contents, as
well as antioxidant activity, increased proportionally to the amount of onion
juice added. Overall, it was confirmed that the addition of onion juice improved
the quality and functionality of Korean soy sauce.
Liver injury in hospitalized patients with COVID-19: An International observational cohort study
Authors: Tirupakuzhi Vijayaraghavan Bharath Kumar , Bishnu Saptarshi , Baruch Joaquin , Citarella Barbara Wanjiru , Kartsonaki Christiana , Meeyai Aronrag , Mohamed Zubair , Ohshimo Shinichiro , Lefèvre Benjamin , Al-Fares Abdulrahman , Calvache Jose A. , Taccone Fabio Silvio , Olliaro Piero , Merson Laura , Adhikari Neill KJ ,   the ISARIC Clinical Characterisation Group
Published: November 2022

Background

Using a large dataset, we evaluated prevalence and severity of alterations in liver enzymes in COVID-19 and association with patient-centred outcomes.

Methods

We included hospitalized patients with confirmed or suspected SARS-CoV-2 infection from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) database. Key exposure was baseline liver enzymes (AST, ALT, bilirubin). Patients were assigned Liver Injury Classification score based on 3 components of enzymes at admission: Normal; Stage I) Liver injury: any component between 1-3x upper limit of normal (ULN); Stage II) Severe liver injury: any component >= 3x ULN. Outcomes were hospital mortality, utilization of selected resources, complications, and durations of hospital and ICU stay. Analyses used logistic regression with associations expressed as adjusted odds ratios (OR) with 95% confidence intervals (CI).

Results

Of 17,531 included patients, 46.2% (8099) and 8.2% (1430) of patients had stage 1 and 2 liver injury respectively. Compared to normal, stages 1 and 2 were associated with higher odds of mortality (OR 1.53 [1.37-1.71]; OR 2.50 [2.10-2.96]), ICU admission (OR 1.63 [1.48-1.79]; OR 1.90 [1.62-2.23]) and invasive mechanical ventilation (OR 1.43 [1.27-1.70]; OR 1.95 (1.55-2.45).Stages 1 and 2 were also associated with higher odds of developing sepsis (OR 1.38 [1.27-1.50]; OR 1.46 [1.25-1.70]), acute kidney injury (OR 1.13 [1.00-1.27]; OR 1.59 [1.32-1.91]), and acute respiratory distress syndrome (OR 1.38 [1.22-1.55]; OR 1.80 [1.49-2.17]).

Conclusions

Liver enzyme abnormalities are common among COVID-19 patients and associated with worse outcomes.

Study Highlights

What is known?

Abnormalities in liver enzymes in hospitalized patients with COVID-19 have been described in small, predominantly single-centre studies.

Impact of such derangements on clinical outcomes are unclear.

What is new here?

In this large international study, we found that close to 50% of hospitalized patients with COVID-19 have abnormal liver enzymes at admission.

Such derangements in liver enzymes are associated with worse clinical outcomes (survival, Intensive Care Unit admission and need for invasive mechanical ventilation).

They are also associated with the development of complications such as Acute Kidney Injury, Sepsis and Acute Respiratory Distress Syndrome.
Comparison of the reactogenicity and immunogenicity between two-dose mRNA COVID-19 vaccine and inactivated followed by an mRNA vaccine in children aged 5 - 11 years
Authors: Wanlapakorn Nasamon , Kanokudom Sitthichai , Phowatthanasathian Harit , Chansaenroj Jira , Suntronwong Nungruthai , Assawakosri Suvichada , Yorsaeng Ritthideach , Nilyanimit Pornjarim , Vichaiwattana Preeyaporn , Klinfueng Sirapa , Thongmee Thanunrat , Aeemjinda Ratchadawan , Khanarat Nongkanok , Srimuan Donchida , Thatsanatorn Thaksaporn , Sudhinaraset Natthinee , Poovorawan Yong
Published: November 2022

Objective

To compare the reactogenicity and immunogenicity between the two-dose mRNA COVID-19 vaccine regimen and one or two doses of inactivated vaccine followed by an mRNA vaccine regimen in healthy children between 5-11 years of age.

Methods

A prospective cohort study was performed at King Chulalongkorn Memorial Hospital in Thailand between March to June 2022. Healthy children between 5-11 years of age were enrolled and received the two-dose mRNA COVID-19 vaccine (BNT162b2) regimen or the inactivated (CoronaVac) vaccine followed by the BNT162b2 vaccine regimen. In addition, healthy children who received two doses of BBIBP-CorV between 1-3 months prior were enrolled to receive a heterologous BNT162b2 as a third dose (booster).

Reactogenicity was assessed by a self-reported online questionnaire. Immunogenicity analysis was performed to determine binding and surrogate neutralizing antibodies to SARS-CoV-2 wild-type and Omicron variants.

Results

Overall, 166 eligible children were enrolled. Local and systemic AE which occurred within 7 days after vaccination were mild to moderate and well-tolerated. At one-month, post-two or post-three doses, children vaccinated with two-dose BNT162b2, CoronaVac/BNT162b2, and two-dose BBIBP-CorV followed by BNT162b2 elicited similar levels of anti-receptor-binding domain (RBD) IgG. However, the two-dose BNT162b2 and two-dose BBIBP-CorV followed by BNT162b2 groups elicited higher neutralizing activities against Omicron BA.2 variant than the CoronaVac/BNT162b2 group.

Conclusion

The heterologous, CoronaVac vaccine followed by the BNT162b2 vaccine, regimen elicited lower neutralizing activities against the emerging Omicron BA.2 variant than the two-dose mRNA regimen. A third dose (booster) mRNA vaccine should be prioritized for this group.
Flexible, Scalable, High Channel Count Stereo-Electrode for Recording in the Human Brain
Authors: Lee Keundong , Paulk Angelique C. , Ro Yun Goo , Cleary Daniel R. , Tonsfeldt Karen J. , Kfir Yoav , Pezaris John , Tchoe Youngbin , Lee Jihwan , Bourhis Andrew M. , Vatsyayan Ritwik , Martin Joel R. , Russman Samantha M. , Yang Jimmy C. , Baohan Amy , Richardson R. Mark , Williams Ziv M. , Fried Shelley I. , Sang U Hoi , Raslan Ahmed M. , Ben-Haim Sharona , Halgren Eric , Cash Sydney S. , Dayeh Shadi. A.
Published: November 2022

Over the past decade, stereotactically placed electrodes have become the gold standard for deep brain recording and stimulation for a wide variety of neurological and psychiatric diseases. Current electrodes, however, are limited in their spatial resolution and ability to record from small populations of neurons, let alone individual neurons. Here, we report on a novel, reconfigurable, monolithically integrated human-grade flexible depth electrode capable of recording from up to 128 channels and able to record at a depth of 10 cm in brain tissue. This thin, stylet-guided depth electrode is capable of recording local field potentials and single unit neuronal activity (action potentials), validated across species. This device represents a major new advance in manufacturing and design approaches which extends the capabilities of a mainstay technology in clinical neurology.

One-Sentence Summary

A human-grade thin-film depth electrode offers new opportunities in spatial and temporal resolution for recording brain activity.
A nematode model to evaluate microdeletion phenotype expression
Authors: Antkowiak Katianna R. , Coskun Peren , Noronha Sharon T. , Tavella Davide , Massi Francesca , Ryder Sean P.
Published: November 2022

Microdeletion syndromes are genetic diseases caused by chromosomal deletions too small to be detected by karyotyping. They are typified by complex pleiotropic developmental phenotypes that depend both on the extent of the deletion and variations in genetic background. Microdeletion alleles disrupt several genes simultaneously, often as the result of a single mutagenic event, causing a wide array of consequences across multiple systems involving multiple pathways. How simultaneous haploinsufficiency of numerous adjacent genes leads to complex and variable pleiotropic phenotypes is not well understood. CRISPR/Cas9 genome editing has been shown to induce microdeletion-like alleles at a meaningful rate. Here, we describe a microdeletion allele inCaenorhabditis elegansrecovered during a CRISPR/Cas9 genome editing experiment. We mapped the allele to chromosome V, balanced it with a reciprocal translocation crossover suppressor, and precisely defined the breakpoint junction. The allele simultaneously removes 32 protein-coding genes, yet animals homozygous for this mutation are viable as adults. Homozygous animals display a complex phenotype including maternal effect lethality, producing polynucleated embryos that grow into uterine tumors, vulva morphogenesis defects, body wall distensions, uncoordinated movement, and a shortened life span typified by death by bursting. Our work provides an opportunity to explore the complexity and penetrance of microdeletion phenotypes in a simple genetic model system.
Quantitative imaging of gene therapy delivery vehicles using CEST-NMR/MRI
Authors: Lam Bonnie , Velasquez Mark , Velasquez-Mao A.J. , Godines Kevin , AlGhuraibawi Wissam , Wendland Michael , Pelton Jeff , Vandsburger Moriel
Published: November 2022

Purpose

Gene therapy employing AAV vector-mediated gene delivery has undergone substantial growth in recent years with promising results in both preclinical and clinical studies, as well as emerging regulatory approval. However, the lack of methods for quantifying the efficacy of gene therapy from cellular delivery of gene editing technology to specific functional outcomes remains an obstacle for the efficient development of gene therapy treatments. Building upon prior works that utilized a genetically encoded Lysine Rich Protein as a chemical exchange saturation transfer (CEST) reporter, we hypothesized that AAV viral capsids may generate endogenous CEST contrast from the large number of surface lysine residues.

Methods

Water-suppressed NMR and NMR-CEST experiments were performed on isolated solutions of AAV serotypes 1-9 on a Bruker 800MHz vertical scanner. A series of in vitro experiments were performed for thorough testing of NMR-CEST contrast of AAV2 capsids under varying pH, density, biological transduction stage, and later across multiple serotypes and mixed biological media. Reverse transcriptase (RT)-polymerase chain reaction (PCR) was used to quantify virus concentration. Subsequent experiments determined the pH-dependent exchange rate and optimized CEST saturation schemes for AAV contrast detection at 7 T.

Results

NMR-CEST experiments revealed CEST contrast up to 52% for AAV2 viral capsids between 0.6-0.8 ppm. Evaluation of CEST contrast generated by AAV2 demonstrates high levels of CEST contrast across a variety of chemical environments, concentrations, and saturation schemes. AAV2 CEST contrast displayed significant positive correlations with capsid density (R2>0.99, P<0.001), pH (R2=0.97, P=0.01), and viral titer per cell count (R2=0.92, P<0.001). Transition to a preclinical field strength yielded up to 11.8% CEST contrast following optimization of saturation parameters.

Conclusion

AAV2 viral capsids exhibit strong capacity as an endogenous CEST contrast agent and can potentially be used for monitoring and evaluation of AAV vector-mediated gene therapy protocols.
Anin vitromicrofluidic culture device for peripheral neurotoxicity prediction at low concentration based on deep learning
Authors: Han Xiaobo , Matsuda Naoki , Matsuda Kazuki , Yamanaka Makoto , Suzuki Ikuro
Published: November 2022

In this study, a microfluidic culture device was developed including related evaluation methods using deep learning for the purpose of constructing a rapid assessment platform for peripheral neuropathy caused by compounds. Primary rodent dorsal root ganglion was cultured in the microfluidic culture device that could separate the cell body and neurites, and the neurites’ morphological changes were analyzed by immunofluorescence images. Separated neurites successful culture in the microfluidic device for more than 1 month indicated that a series of test processes from culture to drug stimulation and fluorescence observation is possible. Additionally, cultured samples were treated with several anticancer drugs known to cause peripheral neurotoxicity (i.e., vincristine, oxaliplatin, and paclitaxel) and analyzed the neurites’ morphological changes by deep learning for image analysis. After training, artificial intelligence (AI) could identify neurite morphological changes caused by each compound and precisely predicted the toxicity positivity, even at low concentrations. For testing compounds, AI could also precisely detect toxicity negative and positive based on neurite images, even at low concentrations. Therefore, this microfluidic culture system is supposed to be useful forin vitrotoxicity assessment.
Identification of a unique transcriptomic signature associated with islet amyloidosis
Authors: Barovic Marko , Steinmeyer Klaus , Kipke Nicole , Schöniger Eyke , Friedland Daniela , Marzetta Flavia , Forberger Almuth , Baretton Gustavo , Weitz Jürgen , Aust Daniela , Ibberson Mark , Distler Marius , Schulte Anke M , Solimena Michele
Published: November 2022

Aims

This cross-sectional study aims to identify potential transcriptomic changes conveyed by presence of amyloid deposits in islets from pancreatic tissue obtained from metabolically profiled living donors.

Methods

After establishing Thioflavin S as the most sensitive approach to detect islet amyloid plaques, we utilized RNA sequencing data obtained from laser capture microdissected islets to define transcriptomic effects of this pathological entity. The RNA sequencing data was used to identify differentially expressed genes by linear modeling. Further analyses included functional enrichment analysis of KEGG and Hallmark gene sets as well as a weighted gene correlation network analysis.

Results

Eleven differentially expressed genes were identified in islets affected by amyloidosis. Enrichment analyses pointed to signatures related to protein aggregation diseases, energy metabolism and inflammatory response. A gene co-expression module was identified that correlated to islet amyloidosis.

Conclusion

Although the influence of underlying Type 2 diabetes could not be entirely excluded, this study presents a valuable insight into the biology of islet amyloidosis, particularly providing hints into the potential relationship between islet amyloid deposition and structural and functional proteins involved in insulin secretion.

Research in context

What is already known about this subject?

Islet amyloidosis is the only histological marker of Type 2 diabetes in the pancreas

Individuals not suffering from Type 2 diabetes can also be affected by islet amyloidosis

The clinicopathological significance of this phenomenon is still unclear

What is the key question?

Does the islet transcriptome of individuals with islet amyloidosis provide explanations for the onset of this phenomenon and its pathophysiological value?

What are the new findings?

Islet transcriptomes of affected subjects exhibit only limited transcriptomic differences compared to unaffected ones.

Structural and functional proteins involved in insulin secretion machinery may be involved in the pathophysiological sequence of amyloid formation
Conceptual structure and current trends in Artificial Intelligence, Machine Learning, and Deep Learning research in sports: A bibliometric review
Authors: Dindorf Carlo , Bartaguiz Eva , Gassmann Freya , Fröhlich Michael
Published: November 2022

Artificial intelligence and its subcategories of machine learning and deep learning are gaining increasing importance and attention in the context of sports research. This has also meant that the number of corresponding publications has become complex and unmanageably large in human terms. In the current state of the research field, there is a lack of bibliometric analysis, which would prove useful for obtaining insights into the large amounts of available literature. Therefore, the present work aims to identify important research issues, elucidate the conceptual structure of the research field, and unpack the evolutionary trends and the direction of hot topics regarding key themes in the research field of artificial intelligence in sports. Using the Scopus database, 1215 documents (reviews and articles) were selected. Bibliometric analysis was performed using VOSviewer and bibliometrix R package. The main findings are as follows: (a) the literature and research interest concerning AI and its subcategories is growing exponentially; (b) the top 20 most cited works comprise 32.52% of the total citations; (c) the top 10 journals are responsible for 28.64% of all published documents; (d) strong collaborative relationships are present, as along with small, isolated collaboration networks of individual institutions; (e) the three most productive countries are China, the USA, and Germany; (f) different research themes can be characterized using author keywords with current trend topics, e.g., in the fields of biomechanics, injury prevention or prediction, new algorithms, and learning approaches. AI research activities in the fields of sports pedagogy, sports sociology, and sports economics seem to have played a subordinate role thus far. Overall, the findings of this study expand knowledge on the research situation as well as the development of research topics regarding the use of artificial intelligence in sports, and may guide researchers to identify currently relevant topics and gaps in the research.
Genebank genomics allows greatly improved taxonomic correction forCapsicum spp. accessions using a novel automated classification method
Authors: Rabanus-Wallace M. Timothy , Stein Nils
Published: November 2022

To maximise the benefit of exploiting genebank resources, accurate and complete taxonomic assignments are imperative. The rise of genebank genomics allows genetic methods to be used for this task, but these need to be largely automated since the number of samples dealt with is too great for efficient manual recategorisation, but no clearly optimal method has yet arisen. A recent landmark genebank genomic study sequenced over 10,000 accessions of peppers (Capsicum spp.), for which the exploitation of genebank material is of huge commercial, cultural, and scientific importance. This study resulted in precisely the type of dataset that will, in coming decades, be likely be produced for hundreds of plant taxa. The long-appreciated difficulties of pepper taxonomy are evident from the many obvious misclassifications noted in this and other studies, providing a perfect opportunity to simultaneously advance methods development in the area, to correct many genebank taxonomic assignments of pepper accessions, and to provide insights into pepper taxonomy in general. This paper aims to achieve these goals using an approach that combines several ideas from standard classification algorithms to create a highly flexible and customisable classifier that performs favourably when compared with key alternative methods. The various characteristics of different methods are discussed, and possible sensible alterations to pepper taxonomy based on the results are proposed for discussion by the community.
Using Haplotype and QTL Analysis to Fix Favorable Alleles in Diploid Potato Breeding
Authors: Song Lin , Endelman Jeffrey B.
Published: November 2022

At present, the potato of international commerce is autotetraploid, and the complexity of this genetic system creates limitations for breeding. Diploid potato breeding has long been used for population improvement, and thanks to improved understanding of the genetics of gametophytic self-incompatibility, there is now sustained interest in the development of uniform F1hybrid varieties based on inbred parents. We report here on the use of haplotype and QTL analysis in a modified backcrossing (BC) scheme, using primary dihaploids ofS.tuberosumas the recurrent parental background. In Cycle 1 we selected XD3-36, a self-fertile F2clone homozygous for the self-compatibility geneSli. Signatures of gametic and zygotic selection were observed at multiple loci in the F2generation, includingSli. In the BC1cycle, an F1population derived from XD3-36 showed a bimodal response for vine maturity, which led to the identification of late vs. early alleles in XD3-36 for the geneStCDF1(Cycling DOF Factor 1). Greenhouse phenotypes and haplotype analysis were used to select a vigorous and self-fertile F2individual with 43% homozygosity, including forSliand the early-maturing alleleStCDF1.3. Partially inbred lines from the BC1and BC2cycles have been used to initiate new cycles of selection, with the goal of reaching higher homozygosity while maintaining plant vigor, fertility, and yield.

Core Ideas

Partially inbred, diploid potato lines were developed for transitioning to an inbred-hybrid breeding system.

Multi-generational linkage analysis was used to track and fix favorable alleles without haplotype-specific markers.

Signatures of gametic and zygotic selection were detected by maximum likelihood.
Survivin is a mechanosensitive cell cycle regulator in vascular smooth muscle cells
Authors: Biber John C. , Sullivan Andra , Brazzo Joseph A. , Krajnik Amanda , Heo Yuna , Poppenberg Kerry E. , Tutino Vincent M. , Heo Su-Jin , Kolega John , Lee Kwonmoo , Bae Yongho
Published: November 2022

Stiffened arteries are a pathology of atherosclerosis, hypertension, and coronary artery disease and a key risk factor for cardiovascular disease events. The increased stiffness of arteries triggers the hypermigration and hyperproliferation of vascular smooth muscle cells (VSMCs), leading to neointimal hyperplasia and accelerated neointima formation, but the mechanism of this trigger is not known. Our analyses of whole-transcriptome microarray data sets from mouse VSMCs cultured on stiff hydrogels simulating arterial pathology and from injured mouse femoral arteries revealed 80 genes that were differentially regulated (74 upregulated and 6 downregulated) relative to expression in control VSMCs cultured on soft hydrogels and in uninjured femoral arteries. A functional enrichment analysis revealed that these stiffness-sensitive genes are linked to cell cycle progression and proliferation. Furthermore, we found that survivin, a member of the inhibitor of apoptosis protein family, mediates stiffness-sensitive cell cycling and proliferationin vivoandin vitroas determined by gene network and pathway analyses, RT-qPCR, and immunoblotting. The stiffness signal is mechanotransduced via FAK and Rac signaling to regulate survivin expression, establishing a regulatory pathway for how the stiffness of the cellular microenvironment affects VSMC behaviors. Our findings indicate that survivin is necessary for VSMC cycling and proliferation and regulates stiffness-responsive phenotypes.
Fly-scan-oriented motion analyses and upgraded beamline integration architecture for the High-Dynamic Double-Crystal Monochromator at Sirius/LNLS
Authors: Geraldes Renan Ramalho , Luiz Sergio Augusto Lordano , de Brito Neto João Leandro , Soares Telles René Silva , dos Reis Ricardo Donizeth , Calligaris Guilherme A. , Witvoet Gert , Vermeulen J. P. M. B.
Published: November 2022

The High-Dynamic Double-Crystal Monochromator (HD-DCM) is a mechatronic system with unique control-based architecture and deep paradigm changes as compared with traditional beamline monochromators. Aiming at unprecedented inter-crystal positioning stability in vertical-bounce double-crystal monochromators (DCMs) of the order of 10 nrad RMS (1 Hz to 2.5 kHz), and not only in fixed-energy but also in fly-scan operation, it has been developed according to a `first-time right' predictive design approach for hard X-ray beamlines at Sirius, the fourth-generation light source at the Brazilian Synchrotron Light Laboratory (LNLS/CNPEM). This work explores some of the challenges that emerge with this new technology and presents the latest commissioning results that demonstrate the unparallel performances of the HD-DCM at the undulator-based EMA (Extreme Methods of Analysis) beamline at Sirius. With the enabled fast spectroscopy fly-scan possibilities, a new energy-tuning evaluation method, based on wave-propagation simulations, becomes part of a motion-oriented analysis that is carried out to derive the multi-axis non-linear positioning problem, covering not only energy selection and fixed exit in the HD-DCM but also the emission spectrum of an adjustable-phase undulator (APU). The HD-DCM control scheme and its flexible operation modes are described in detail as well. Furthermore, a new integration topology between the HD-DCM and EMA's APU, coming already close to ultimate motion levels, is described and validated.
FOCUS: fast Monte Carlo approach to coherence of undulator sources
Authors: Siano M. , Geloni G. , Paroli B. , Butti D. , Lefèvre T. , Mazzoni S. , Trad G. , Iriso U. , Nosych A. A. , Torino L. , Potenza M. A. C.
Published: November 2022

FOCUS (Fast Monte CarlO approach to Coherence of Undulator Sources) is a new GPU-based simulation code to compute the transverse coherence of undulator radiation from ultra-relativistic electrons. The core structure of the code, which is written in the language C++ accelerated with CUDA, combines an analytical description of the emitted electric fields and massively parallel computations on GPUs. The combination is rigorously justified by a statistical description of synchrotron radiation based on a Fourier optics approach. FOCUS is validated by direct comparison with multi-electron Synchrotron Radiation Workshop (SRW) simulations, evidencing a reduction in computation times by up to five orders of magnitude on a consumer laptop. FOCUS is then applied to systematically study the transverse coherence in typical third- and fourth-generation facilities, highlighting peculiar features of undulator sources close to the diffraction limit. FOCUS is aimed at fast evaluation of the transverse coherence of undulator radiation as a function of the electron beam parameters, to support and help prepare more advanced and detailed numerical simulations with traditional codes like SRW.
Fully automated multi-grid cryoEM screening using Smart Leginon
Authors: Cheng Anchi , Kim Paul T. , Kuang Huihui , Mendez Joshua H. , Chua Eugene Y. D. , Maruthi Kashyap , Wei Hui , Sawh Anjelique , Aragon Mahira F. , Serbynovskyi Viacheslav , Neselu Kasahun , Eng Edward T. , Potter Clinton S. , Carragher Bridget , Bepler Tristan , Noble Alex J.
Published: November 2022

Single-particle cryo-electron microscopy (cryoEM) is a swiftly growing method for understanding protein structure. With increasing demand for high-throughput, high-resolution cryoEM services comes greater demand for rapid and automated cryoEM grid and sample screening. During screening, optimal grids and sample conditions are identified for subsequent high-resolution data collection. Screening is a major bottleneck for new cryoEM projects because grids must be optimized for several factors, including grid type, grid hole size, sample concentration, buffer conditions, ice thickness and particle behavior. Even for mature projects, multiple grids are commonly screened to select a subset for high-resolution data collection. Here, machine learning and novel purpose-built image-processing and microscope-handling algorithms are incorporated into the automated data-collection software Leginon, to provide an open-source solution for fully automated high-throughput grid screening. This new version, broadly called Smart Leginon, emulates the actions of an operator in identifying areas on the grid to explore as potentially useful for data collection. Smart Leginon Autoscreen sequentially loads and examines grids from an automated specimen-exchange system to provide completely unattended grid screening across a set of grids. Comparisons between a multi-grid autoscreen session and conventional manual screening by 5 expert microscope operators are presented. On average, Autoscreen reduces operator time from ∼6 h to <10 min and provides a percentage of suitable images for evaluation comparable to the best operator. The ability of Smart Leginon to target holes that are particularly difficult to identify is analyzed. Finally, the utility of Smart Leginon is illustrated with three real-world multi-grid user screening/collection sessions, demonstrating the efficiency and flexibility of the software package. The fully automated functionality of Smart Leginon significantly reduces the burden on operator screening time, improves the throughput of screening and recovers idle microscope time, thereby improving availability of cryoEM services.
Do expressions of sadness, anxiety and fear have different impacts on attracting donations? Evidence from a Chinese online charitable crowdfunding platform
Authors: Ge Ruichen , Zhang Sha , Zhao Hong
Published: November 2022

Purpose

Extant research shows mixed results on the impact of expressed negative emotions on donations in online charitable crowdfunding. This study solves the puzzle by examining how different types of negative emotions (i.e. sadness, anxiety and fear) expressed in crowdfunding project descriptions affect donations.

Design/methodology/approach

Data on 15,653 projects across four categories (medical assistance, education assistance, disaster assistance and poverty assistance) from September 2013 to May 2019 come from a leading online crowdfunding platform in China. Text analysis and regression models serve to test the hypotheses.

Findings

In the medical assistance category, the expression of sadness has an inverted U-shaped effect on donations, while the expression of anxiety has a negative effect. An appropriate number of sadness words is helpful but should not exceed five times. In the education assistance and disaster assistance categories, the expression of sadness has a positive effect on donations, but disclosure of anxiety and fear has no influence on donations. Expressions of sadness, anxiety and fear have no impact on donations in the poverty assistance category.

Research limitations/implications

This work has important implications for fundraisers on how to regulate the fundraisers' expressions of negative emotions in a project's description to attract donations. These insights are also relevant for online crowdfunding platforms.

Originality/value

Online crowdfunding research often studies negative emotions as a whole and does not differentiate project types. The current work contributes by empirically testing the impact of three types of negative emotions on donations across four major online crowdfunding categories.