bluuebunny/crossref_metadata_2025 huggingface dataset:
Openness and Computational Reproducibility in Plant Pathology: Where We Stand and a Way Forward
Authors: Sparks Adam H. , Ponte Emerson M. Del , Alves Kaique S. , Foster Zachary S. L. , Grünwald Niklaus J.
Published: January 2023

Open research practices have been highlighted extensively during the last 10 years in many fields of scientific study as essential standards needed to promote transparency and reproducibility of scientific results. Scientific claims can only be evaluated based on how protocols, materials, equipment, and methods were described; data were collected and prepared; and analyses were conducted. Openly sharing protocols, data, and computational code is central to current scholarly dissemination and communication, but in many fields, including plant pathology, adoption of these practices has been slow. We randomly selected 450 articles published from 2012 to 2021 across 21 journals representative of the plant pathology discipline and assigned them scores reflecting their openness and computational reproducibility. We found that most of the articles did not follow protocols for open science and failed to share data or code in a reproducible way. We propose that use of open-source tools facilitates computationally reproducible work and analyses, benefitting not just readers but the authors as well. Finally, we provide ideas and suggest tools to promote open, reproducible computational research practices among plant pathologists.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
SP1 impacts the primordial to primary follicle transition by regulating cholesterol metabolism in granulosa cells
Authors: Zhou Jiaqi , Lin Lin , Cai Han , Liu Longping , Wang Huarong , Zhang Jingwen , Xia Guoliang , Wang Jianbin , Wang Fengchao , Wang Chao
Published: January 2023

The primordial to primary follicle transition (PPT) in the ovary is critical to maintain sustainable reproductive resources in female mammals. However, it is unclear how granulosa cells (GCs) of the primary follicle participate in regulating PPT. This study focused on exploring the role of transcription factor Sp1 (SP1) in regulating PPT based on the fact that SP1 is pivotal for pregranulosa cell proliferation before primordial follicle formation. The results showed that mice fertility was prolonged when Sp1 was specifically depleted from GCs (GC‐ Sp1 −/−). Besides, the PPT in GC‐ Sp1 −/− mice was reduced, resulting in more primordial follicles being preserved. Single‐cell RNA‐seq also indicated that the level of cholesterol metabolism was downregulated in GC‐ Sp1 −/− mice. Additionally, the PPT was promoted by either overexpression of ferredoxin‐1 (FDX1), one of the key genes in mediating cholesterol metabolism or supplementing cholesterol for cultured fetal ovaries. Collectively, SP1 in GCs participates in the metabolism of cholesterol partially by regulating the transcription of Fdx1 during the PPT.
Fatty acid oxidation fuels agonist‐induced platelet activation and thrombus formation: Targeting β‐oxidation of fatty acids as an effective anti‐platelet strategy
Authors: Kulkarni Paresh P. , Ekhlak Mohammad , Singh Vipin , Kailashiya Vikas , Singh Nitesh , Dash Debabrata
Published: January 2023

Platelet mitochondria possess remarkable plasticity for oxidation of energy substrates, where metabolic dependency on glucose or fatty acids is higher than glutamine. Since platelets metabolize nearly the entire pool of glucose to lactate rather than fluxing through mitochondrial tricarboxylic acid cycle, we posit that majority of mitochondrial ATP, which is essential for platelet granule secretion and thrombus formation, is sourced from oxidation of fatty acids. We performed a comprehensive analysis of bioenergetics and function of stimulated platelets in the presence of etomoxir, trimetazidine and oxfenicine, three pharmacologically distinct inhibitors of β‐oxidation. Each of them significantly impaired oxidative phosphorylation in unstimulated as well as thrombin‐stimulated platelets leading to a small but consistent drop in ATP level in activated cells due to a lack of compensation from glycolytic ATP. Trimetazidine and oxfenicine attenuated platelet aggregation, P‐selectin externalization and integrin αIIbβ3 activation. Both etomoxir and trimetazidine impeded agonist‐induced dense granule release and platelet thrombus formation on collagen under arterial shear. The effect of inhibitors on platelet aggregation and dense granule release was dose‐ and incubation time‐ dependent with significant inhibition at higher doses and prolonged incubation times. Neither of the inhibitors could protect mice from collagen‐epinephrine‐induced pulmonary embolism or prolong mouse tail bleeding times. However, mice pre‐administered with etomoxir, trimetazidine and oxfenicine were protected from ferric chloride‐induced mesenteric thrombosis. In conclusion, β‐oxidation of fatty acids sustains ATP level in stimulated platelets and is therefore essential for energy‐intensive agonist‐induced platelet responses. Thus, fatty acid oxidation may constitute an attractive therapeutic target for novel antiplatelet agents.
Mpox (Monkeypox) Presenting as Cervical and Vulvar Disease
Authors: Ramírez Mar , Delso Vanesa , Sánchez María J. , Sagastagoitia Íñigo , Vargas Sara , García Alejandro , Coronado Pluvio J.
Published: January 2023

BACKGROUND:

Since the beginning of the current mpox (formerly “monkeypox”) outbreak in May 2022, 23,465 confirmed cases of monkeypox virus infection have been reported in Europe; women represent less than 1% of these cases. Mpox lesions are found with greater frequency in the genital area, and, in women, have been described primarily in the vulva.

CASE:

We present a case of monkeypox virus infection in a 28-year-old woman confirmed by polymerase chain reaction testing, in which the only clinical manifestation was the appearance of concomitant lesions in the cervix and the vulva, with no other clinical features. No other sexual transmitted diseases were found. The lesions disappeared spontaneously in 2 weeks.

CONCLUSION:

Mpox lesions can affect the cervix; thus, recognition by gynecologists is important. Given the current epidemic outbreak, correct identification is essential to help control disease transmission.
Psoriasis-Like Lesions Secondary to SARS-CoV-2 Infection
Authors: Geremia Nicholas , Gunnella Susanna
Published: January 2023

In 2019, the first case of severe acute respiratory syndrome coronavirus 2 pneumoniae was reported in Wuhan, People's Republic of China. Severe acute respiratory syndrome coronavirus 2 can involve different organ systems, including the skin. Twenty percent of patients in an Italian medical ward had cutaneous manifestations. We described a 65-year-old White woman who developed not itchy, not painful, erythematous, slightly infiltrated plaques characterized by fine desquamation and localized at the extremities secondary to severe acute respiratory syndrome coronavirus 2 infection. Local treatment with calcipotriene and betamethasone dipropionate was started with clinical response. The close association with Coronavirus disease diagnosis and the clinical response to calcipotriene and local steroid therapy suggested psoriasis-like eruption secondary to SARS-CoV-2 infection.
Cytomegalovirus Anterior Uveitis in an Immunocompetent Patient
Authors: Sullivan Michael Blade , Veresciac Anastasia , Bush Larry M.
Published: January 2023

Most cases of uveitis involve the anterior compartment with resultant iritis, cyclitis, or iridocyclitis. Usually, they are either associated with an autoimmune condition or relegated as idiopathic. Approximately 10% of the time an infectious disease etiology is determined to be the cause, in which case, herpes simplex virus and less often varicella zoster virus are the pathogens. Traditionally, cytomegalovirus ocular infections present with retinitis or acute retinal necrosis and almost always in immunocompromised hosts (eg, AIDS), We present a case of chronic cytomegalovirus anterior uveitis in an immunocompetent man diagnosed only after failing the treatment of presumed herpes simplex virus infection and the epidemiology, proposed mechanism of infection, clinical manifestations, diagnostic tests, and treatment of this less well-recognized infection in patients with adequate immune systems.
Gastric Polyp
Authors: Ganapule Avinash A. , Hegde Aniketh , Kumar Vijay , Kumar Tarun , Bhushan Divendu
Published: January 2023

Mucormycosis is usually an infection of immunocompromised patients. In the COVID-19 pandemic, its incidences increased due to immunocompromised states and injudicious use of steroids. It usually causes sinusitis and orbital involvement and may extend to the brain causing life-threatening condition. Involvement of gastrointestinal tract is rare. The stomach is the most commonly involved part followed by colon and ileum. It is mostly a part of disseminated disease.

Here we are describing a case of dyspepsia that was diagnosed to have rare fungal infection without involving other usual sites.
Microvirgula curvata as a Cause of Ventriculoperitoneal Shunt Infection
Authors: Miceli Madeline , Ogulnick Jonathan , Gnanaprakasam Rachel , Belal Maymonah
Published: January 2023

Microvirgula curvata is a small Gram-negative, curved rod first isolated from hydrocarbon-contaminated soil in Kuwait (Subhash et al. Int J Syst Evol Microbiol 2016;66:5309–5313). We describe the first known case of human infection with M. curvata in a 65-year-old man with a ventriculoperitoneal shunt.
Relationship Between Sensory Organization Testing Scores With Lower Extremity Injuries and Prior Concussion in Professional Soccer Players
Authors: Mooney James , Cochrane Graham D. , Gould Sara
Published: January 2023

Objective:

To evaluate for associations between concussion history or lower extremity (LE) injury and computerized sensory organization testing (SOT) performance in professional soccer players.

Design:

Cross-sectional study.

Setting:

Tertiary care center.

Participants:

Thirty-three, professional, male soccer players on an American club, between the years 2019 and 2021.

Assessment of Risk Factors:

Player age, history of reported LE injury (gluteal, hamstring, ankle, knee, hip, groin, and sports hernia), history of diagnosed concussion, and the number of prior concussions were documented for each player.

Main Outcome Measures:

Baseline SOT of postural sway was conducted in 6 sensory conditions for all players.

Results:

Eleven athletes (33%) reported a previous concussion, and 15 (45%) reported a previous LE injury. There were no significant differences in SOT scores between those with and without a previous diagnosis of concussion (P > 0.05). Those reporting a previous LE injury performed better on condition 3 (eyes open, unstable visual surround) than those who did not (P = 0.03). Athletes aged 25 years or younger performed worse on condition 3 (P = 0.01) and had worse, although not statistically significant, median performance on all other balance measures than those older than 25 years. Intraclass correlation coefficient for repeat SOT assessment was 0.58, indicating moderate reliability, without an evident practice effect.

Conclusions:

Professional soccer players with a previous concussion or history of LE injury did not demonstrate long-term deficits in postural control, as assessed by multiyear computerized SOT baseline testing. The SOT was reliable over time with younger athletes exhibiting greater postural sway than older athletes.
Cardiovascular Risk Factors and Sudden Sensorineural Hearing Loss: A Case-Control Study
Authors: Lenkeit Christopher P. , Lofgren Daniel H. , Zappia John
Published: January 2023

Objective

To investigate the role of cardiovascular risk factors (specifically hypertension [HTN], hyperlipidemia/dyslipidemia, diabetes mellitus I and II, and body mass index (BMI) on the development of sudden sensorineural hearing loss (SSNHL).

Study Design

Case-control retrospective chart review.

Setting

A tertiary referral center.

Patients

Patients aged 18 to 85 years who presented to the clinic over a 1-year span (September 17, 2020 to September 17, 2021) for evaluation of sudden sensorineural hearing loss.

Main Outcome Measure

Comparing the prevalence of the different cardiovascular risk factors (CVRFs) in patients with sudden sensorineural hearing loss compared with when compared with non-SSNHL patients at a neurotology clinic.

Results

Two hundred twenty-three patients with SSNHL were compared with age- and gender-matched comparison group to investigate the prevalence of cardiovascular risk factors within each group. There are no statistically significant differences (p > 0.05) in the prevalence of HTN, hyperlipidemia/dyslipidemia, diabetes mellitus I and II, and BMI in patients with sudden sensorineural hearing loss when compared with non-SSNHL patients at a neurotology clinic.

Conclusions

Despite correlation between CVRF and SSNHL found in some other studies, we did not find a significant correlation between CVRF (diabetes, HTN, dyslipidemia, and high BMI) and SSNHL in our retrospective case control study of patients presenting to a nonacademic tertiary neurotology clinic. Although there may be other factors contributing to the pathogenesis of SSNHL, we have not yet identified these factors.
Creative Arts Therapy Among Children With Cancer
Authors: Raybin Jennifer L. , Zhou Wenru , Pan Zhaoxing , Hendricks-Ferguson Verna L. , Jankowski Catherine
Published: January 2023

Background

Symptom distress is related to decreased quality of life (QOL) among children with cancer, with high levels of pain, nausea, and anxiety reported. Creative arts therapy (CAT) has been related to improved QOL and symptoms in pediatric oncology, but the quality of evidence is mixed.

Objective

This article aims to examine the QOL symptom subscales in relation to CAT over time in children during the first year of cancer treatment.

Methods

A secondary analysis of prospective data was performed with linear mixed modeling on 267 observations with predictors of 2 groups: No CAT (n = 18) vs CAT (n = 65). The covariate of time (6 months) was used to explore the CAT relationship with the Pediatric Quality of Life Inventory (PedsQL) symptom subscales (pain and hurt, nausea, procedural anxiety, treatment anxiety, worry, cognitive problems, perceived physical appearance, and communication).

Results

Children (n = 83) were between 3 and 17 years old (M = 6), 51.2% female, and 32% minority. All tumor types were represented: liquid (37.3%), solid (24.1%), and central nervous system (38.6%). Reduced child report of procedural anxiety was significantly related to receiving CAT with a medium magnitude of association (adjusted effect size = 0.58, P = .01).

Conclusion

Creative arts interventions were associated with a longitudinal improvement in anxiety in children with cancer. Further work is needed to target interventions to the appropriate specific burdensome symptoms.

Implication for Practice

Pediatric oncology nurses can advocate for CAT as an effective intervention to ameliorate the burdensome procedural anxiety experienced by patients.
The Effect of Mindfulness-Based Stress Reduction (MBSR) on Emotional Flexibility and Ambivalence Over Emotional Expression in Divorced Women
Authors: Heshmati Rasoul , Khoury Bassam , Azmoodeh Shahin , Zerang Masoumeh , Sadowski Isabel
Published: January 2023

The present study was developed to evaluate the effects of mindfulness-based stress reduction (MBSR) on the level of emotional flexibility and ambivalence related to emotional expression of divorced women. A general community sample of 30 divorced women was recruited and randomly assigned to experimental and control groups. The experimental group received MBSR for 8 weeks, and the control group was placed on a waiting list. The Emotional Flexibility Questionnaire (EFQ) and the Ambivalence Over the Expression of Emotion Questionnaire (AEQ) were administered to both groups before (pre) and after (post) the treatment. Data were analyzed using two-way mixed repeated-measures analyses of variance. The results showed that women in the treatment group had a significant increase in the total score of the EFQ and its components. In addition, the MBSR group had a significant decrease in the total score of the AEQ and its components. MBSR intervention shows potential for use with divorced women to help with emotion regulation and subsequent better adjustment to separation.
CD4/CD8 Ratio Recovery Among People Living With HIV Starting With First-Line Integrase Strand Transfer Inhibitors: A Prospective Regional Cohort Analysis
Authors: Han Win Min , Avihingsanon Anchalee , Rajasuriar Reena , Tanuma Junko , Mundhe Sanjay , Lee Man-Po , Choi Jun Yong , Pujari Sanjay , Chan Yu-Jiun , Somia Agus , Zhang Fujie , Kumarasamy Nagalingeswaran , Tek NG Oon , Gani Yasmin , Chaiwarith Romanee , Pham Thach Ngoc , Do Cuong Duy , Ditangco Rossana , Kiertiburanakul Sasisopin , Khol Vohith , Ross Jeremy , Jiamsakul Awachana ,   on behalf of IeDEA Asia‐Pacific
Published: January 2023

Background:

We evaluated trends in CD4/CD8 ratio among people living with HIV (PLWH) starting antiretroviral therapy (ART) with first-line integrase strand transfer inhibitors (INSTI) compared with non-INSTI-based ART, and the incidence of CD4/CD8 ratio normalization.

Methods:

All PLWH enrolled in adult HIV cohorts of IeDEA Asia-Pacific who started with triple-ART with at least 1 CD4, CD8 (3-month window), and HIV-1 RNA measurement post-ART were included. CD4/CD8 ratio normalization was defined as a ratio ≥1. Longitudinal changes in CD4/CD8 ratio were analyzed by linear mixed model, the incidence of the normalization by Cox regression, and the differences in ratio recovery by group-based trajectory modeling.

Results:

A total of 5529 PLWH were included; 80% male, median age 35 years (interquartile range [IQR], 29–43). First-line regimens were comprised of 65% NNRTI, 19% PI, and 16% INSTI. The baseline CD4/CD8 ratio was 0.19 (IQR, 0.09–0.33). PLWH starting with NNRTI- (P = 0.005) or PI-based ART (P = 0.030) had lower CD4/CD8 recovery over 5 years compared with INSTI. During 24,304 person-years of follow-up, 32% had CD4/CD8 ratio normalization. After adjusting for age, sex, baseline CD4, HIV-1 RNA, HCV, and year of ART initiation, PLWH started with INSTI had higher odds of achieving CD4/CD8 ratio normalization than NNRTI- (P < 0.001) or PI-based ART (P = 0.015). In group-based trajectory modeling analysis, INSTI was associated with greater odds of being in the higher ratio trajectory.

Conclusions:

INSTI use was associated with higher rates of CD4/CD8 ratio recovery and normalization in our cohort. These results emphasize the relative benefits of INSTI-based ART for immune restoration.
Prevalence of Potentially Clinically Significant Drug–Drug Interactions With Antiretrovirals Against HIV Over Three Decades: A Systematic Review of the Literature
Authors: Hodge Daryl , Hodel Eva Maria , Hughes Elen , Hazenberg Phoebe , Grañana Castillo Sandra , Gibbons Sara , Wang Duolao , Marra Fiona , Marzolini Catia , Back David , Khoo Saye
Published: January 2023

Background:

Contemporary first-line antiretrovirals have considerably reduced liability for clinically significant drug–drug interactions (DDI). This systematic review evaluates the prevalence of DDI among people receiving antiretrovirals across 3 decades.

Methods:

We searched 3 databases for studies reporting the prevalence of clinically significant DDIs in patients receiving antiretrovirals published between January 1987 and July 2022. Clinically significant DDIs were graded by severity. All data extractions were undertaken by 2 independent reviewers, adjudicated by a third.

Results:

Of 21,665 records returned, 13,474 were duplicates. After screening the remaining 13,596 abstracts against inclusion criteria, 122 articles were included for full-text analysis, from which a final list of 34 articles were included for data synthesis. The proportion of patients experiencing a clinically significant DDI did not change over time (P = 0.072). The most frequently reported classes of antiretrovirals involved in DDIs were protease inhibitors and non-nucleoside reverse transcriptase inhibitors; of note, integrase use in the most recent studies was highly variable and ranged between 0% and 89%.

Conclusions:

The absolute risk of DDIs has not decreased over the period covered. This is likely related to continued use of older regimens and an ageing cohort of patients. A greater reduction in DDI prevalence can be anticipated with broader uptake of regimens containing unboosted integrase inhibitors or non-nucleoside reverse transcriptase inhibitors.
VHL Mutation Drives Human Clear Cell Renal Cell Carcinoma Progression Through PI3K/AKT-Dependent Cholesteryl Ester Accumulation
Authors: Zhang Shuo , Fang Tinghe , He Yexuan , Feng Weichen , Yu Zhuoyang , Zheng Yaoyao , Zhang Chi , Hu Shuai , Liu Zhuojun , Liu Jia , Yu Jian , Zhang Han , He Anbang , Gong Yanqing , He Zhisong , Yang Kaiwei , Xi Zhijun , Yu Wei , Zhou Liqun , Yao Lin , Yue Shuhua
Published: January 2023

Background

Cholesteryl ester (CE) accumulation in intracellular lipid droplets (LDs) is an essential signature of clear cell renal cell carcinoma (ccRCC), but its molecular mechanism and pathological significance remain elusive.

Methods

Enabled by the label-free Raman spectromicroscopy, which integrated stimulated Raman scattering microscopy with confocal Raman spectroscopy on the same platform, we quantitatively analyzed LD distribution and composition at the single cell level in intact ccRCC cell and tissue specimensin situwithout any processing or exogenous labeling. Since we found that commonly used ccRCC cell lines actually did not show the CE-rich signature, primary cancer cells were isolated from human tissues to retain the lipid signature of ccRCC with CE level as high as the original tissue, which offers a preferable cell model for the study of cholesterol metabolism in ccRCC. Moreover, we established a patient-derived xenograft (PDX) mouse model that retained the CE-rich phenotype of human ccRCC.

Findings

Surprisingly, our results revealed that CE accumulation was induced by tumor suppressor VHL mutation, the most common mutation of ccRCC. Moreover, VHL mutation was found to promote CE accumulation by upregulating HIFα and subsequent PI3K/AKT/mTOR/SREBPs pathway. Inspiringly, inhibition of cholesterol esterification remarkably suppressed ccRCC aggressivenessin vitroandin vivowith negligible toxicity, through the reduced membrane cholesterol-mediated downregulations of integrin and MAPK signaling pathways.

Interpretation

Collectively, our study improves current understanding of the role of CE accumulation in ccRCC and opens up new opportunities for treatment.

Funding

This work was supported by National Natural Science Foundation of China (No. U23B2046 and No. 62027824), National Key R&D Program of China (No. 2023YFC2415500), Fundamental Research Funds for the Central Universities (No. YWF-22-L-547), PKU-Baidu Fund (No. 2020BD033), Peking University First Hospital Scientific and Technological Achievement Transformation Incubation Guidance Fund (No.2022CX02), and Beijing Municipal Health Commission (No. 2020-2Z-40713).
The BinaxNOW antigen detection assay on CSF samples for diagnosis of pneumococcal meningitis
Authors: Peela Sreeram Chandra Murthy , Sistla Sujatha
Published: January 2023

Introduction

The BinaxNOW pneumococcal antigen detection assay is an immuno-chromatographic technique where the cell wall polysaccharide instead of capsular polysaccharide is the target. Although intended for use on urine samples, its role in diagnosis of pneumococcal meningitis has been reported by many others. The current study explores its accuracy when compared with real-time PCR.

Methodology

CSF samples from suspected meningitis cases were processed for Gram stain and culture following standard protocols. Antigen was detected by BinaxNOW antigen detection assay forStreptococcus pneumoniae. Previously published primers and protocols were used for real-time PCR targeting autolysin (lytA) gene and was considered as the gold standard test.

Results

Among the 74 samples tested, pneumococcal antigen was detected in 21.6% (16/74) and qPCR in 11 (14.9%) samples. Antigen detection assay had higher sensitivity (90.9%) when compared with culture (45.5%) while the positive predictive value was the lowest (62.5% and 100% for culture). It was in substantial agreement with the gold standard test with kappa coefficient of 0.685 and an accuracy of 90.5%.

Conclusions

The BinaxNOW pneumococcal antigen detection test can be employed for initial screening of samples or point-of-care test owing to its substantial agreement with real-time PCR.
Autophagy disruption reduces mTORC1 activation leading to retinal ganglion cell neurodegeneration associated with glaucoma
Authors: Huang Kang-Chieh , Gomes Cátia , Shiga Yukihiro , Belforte Nicolas , VanderWall Kirstin B. , Lavekar Sailee S. , Fligor Clarisse M. , Harkin Jade , Di Polo Adriana , Meyer Jason S.
Published: January 2023

Autophagy dysfunction has been associated with several neurodegenerative diseases including glaucoma, characterized by the degeneration of retinal ganglion cells (RGCs). However, the mechanisms by which autophagy dysfunction promotes RGC damage remain unclear. Here, we hypothesized that perturbation of the autophagy pathway results in increased autophagic demand, thereby downregulating signaling through mammalian target of rapamycin complex 1 (mTORC1), a negative regulator of autophagy, contributing to the degeneration of RGCs. We identified an impairment of autophagic-lysosomal degradation and decreased mTORC1 signaling via activation of the stress sensor adenosine monophosphate-activated protein kinase (AMPK), along with subsequent neurodegeneration in RGCs differentiated from human pluripotent stem cells (hPSCs) with a glaucoma-associated variant of Optineurin (OPTN-E50K). Similarly, the microbead occlusion model of glaucoma resulting in ocular hypertension also exhibited autophagy disruption and mTORC1 downregulation. Pharmacological inhibition of mTORC1 in hPSC-derived RGCs recapitulated disease-related neurodegenerative phenotypes in otherwise healthy RGCs, while the mTOR-independent induction of autophagy reduced protein accumulation and restored neurite outgrowth in diseased OPTN-E50K RGCs. Taken together, these results highlight an important balance between autophagy and mTORC1 signaling essential for RGC homeostasis, while disruption to these pathways contributes to neurodegenerative features in glaucoma, providing a potential therapeutic target to prevent neurodegeneration.
The impact of the COVID-19 pandemic on Antipsychotic Prescribing in individuals with autism, dementia, learning disability, serious mental illness or living in a care home: A federated analysis of 59 million patients’ primary care records in situ using OpenSAFELY
Authors:   The OpenSAFELY Collaborative:, Macdonald Orla , Green Amelia , Walker Alex , Croker Richard , Curtis Helen , Brown Andrew , Butler-Cole Ben , Andrews Colm , Morton Caroline , Evans Dave , Inglesby Peter , Dillingham Iain , Massey Jon , Fisher Louis , Bacon Seb , Davy Simon , Ward Tom , Hulme Will , Morley Jess , Mehrkar Amir , Bates Chris , Cockburn Jonathan , Parry John , Hester Frank , Harper Sam , O’Hanlon Shaun , Eavis Alex , Jarvis Richard , Avramov Dima , Wood Ian , Parkes Nasreen , Goldacre Ben , MacKenna Brian
Published: January 2023

Background

The COVID-19 pandemic significantly affected health and social care services. We aimed to explore whether this impacted the prescribing rates of antipsychotics within at-risk populations.

Methods

With the approval of NHS England, we completed a retrospective cohort study, using the OpenSAFELY platform to explore primary care data of 59 million patients. We identified patients in five at-risk groups: autism, dementia, learning disability, serious mental illness and care home residents. We then calculated the monthly prevalence of antipsychotic prescribing in the population, as well as the incidence of new prescriptions in each month over the study period (Jan 2019-Dec 2021).

Results

The average monthly rate of antipsychotic prescribing increased in dementia from 82.75 patients prescribed an antipsychotic per 1000 patients (95% CI 82.30-83.19) in Q1 2019 to 90.1 (95% CI 89.68-90.60) in Q4 2021 and from 154.61 (95% CI 153.79-155.43) in Q1 2019 to 166.95 (95% CI 166.23-167.67) in Q4 2021 in care homes. There were notable spikes in the rate of new prescriptions issued to patients with dementia and in care homes. In learning disability and autism groups, the average monthly rate of prescribing per 1000 decreased from 122.97 (95% CI 122.29-123.66) in Q1 2019 to 119.29 (95% CI 118.68-119.91) in Q4 2021, and from 54.91 (95% CI 54.52-55.29) in Q1 2019 to 51.04 (95% CI 50.74-51.35) in Q4 2021 respectively.

Conclusions

During each of the lockdowns in 2020, we observed a significant spike in antipsychotic prescribing in the dementia and care home groups. We have shown that these peaks are likely due to prescribing of antipsychotics for palliative care purposes and may have been linked to pre-emptive prescribing, when on-site medical visits would have been restricted. Over the study period, we observed gradual increases in antipsychotic use in patients with dementia and in care homes and a decrease in their use in patients with learning disability or autism.
How is physical healthcare experienced by staff, service users, and carers in adult community mental health services in a South London Mental Health Trust? A Service Evaluation
Authors: Tredget Gracie , Williams Julie , McGrath Ray , Sadler Euan , Gaughran Fiona , Ang Karen , Stepan Natalia , Cross Sean , Tweed John , Orlando Lia , Sevdalis Nick
Published: January 2023

Background

Adults with a serious mental illness (SMI) are at greater risk of physical health morbidity and premature death than the general population, largely as a result of preventable physical health issues. Staff working in mental health services have a role to play in addressing these inequalities, but little is known about how they perceive their role and how this impacts on their practice. Understanding this better would enable services to improve their approach and support better health outcomes for SMI patients. A service evaluation was undertaken to investigate how physical healthcare is approached within adult community mental health teams (CMHTs) at a South London (UK) Mental Health Trust.

Methods

This was a prospective, cross-sectional evaluation design. Interviews and focus groups were conducted with clinical staff, service users and carers, to understand their experiences and to identify key barriers and facilitators to supporting physical healthcare support for adults with SMI. Thematic analysis was conducted to identify key themes which were classified into five main categories.

Results

50 participants took part in the study, 38 were clinical staff, eight were service users and four were carers. We found staff widely recognised the importance of supporting physical healthcare. However, there was variability in how staff approached physical healthcare in routine practice, and differences in how physical healthcare is experienced by service users and carers. Staff were keen to engage in changes to the way physical healthcare is delivered in CMHTs. However, they sought clearer guidance on their roles and responsibilities, and wanted to better understand the rationale for changes in community mental health practice, such as increased screening for physical healthcare. Service users and carers felt equally that the role of CMHTs in physical healthcare was unclear, which limited their ability to access it and understand the benefit for their overall care. Staff articulated gaps in leadership and training that impacted on their ability to implement the overall vision for physical healthcare within the Trust.

Conclusion

Mental health staff recognise the role they play in supporting the physical health of adults living with SMI. This evaluation provides insight into common barriers and facilitators faced by staff, service users and carers when providing or accessing physical healthcare within adult CMHTs. These findings indicate a more comprehensive and better articulated approach to physical healthcare in mental health Trusts is needed to ensure service users and their carers understand what support is available and how to access it and to equip staff to provide and sustain that care in routine practice.
Cortical projection to the pedunculopontine nucleus subpopulation for the Go/STOP signal modulation of muscle tone and locomotion
Authors: Dautan Daniel
Published: January 2023

This manuscript has been withdrawn at the request of Rutgers University
The neuron mixer and its impact on human brain dynamics
Authors: Luff Charlotte E. , Peach Robert , Mallas Emma-Jane , Rhodes Edward , Laumann Felix , Boyden Edward S. , Sharp David J. , Barahona Mauricio , Grossman Nir
Published: January 2023

A signal mixer made of a transistor or a diode facilitates rich computation, which has been the building block of modern telecommunications. The mixing produces new signals at the sum and difference frequencies of the input, thereby enabling powerful operations such as frequency conversion (aka heterodyning), phase detection, and multiplexing. Here, we report that a neural cell is also a signal mixer. We found throughex-vivoandin-vivowhole-cell measurements that neurons mix exogenous (controlled) and endogenous (spontaneous) subthreshold membrane potential oscillations, producing new oscillation frequencies. We show, using pharmacological manipulation, that the neural mixing originates in the voltage-gated ion channels. Furthermore, we demonstrate that the neural mixing dynamic is evident in human brain activity and is associated with cognitive functions. We found that the human electroencephalogram (EEG) displays distinct clusters of local and inter-region mixing interactions. By quantifying the strength of these interactions before a task, we show that converting the salient posterior alpha-beta oscillations into gamma-band oscillations regulates the visual attention state. Neural circuit oscillations have been observed in nearly every cognitive domain and species, and abnormal spectra of neural oscillations have been found in almost all brain disorders. Signal mixing enables individual neurons to actively sculpt the spectrum of their circuit oscillations and utilize them for computational operations, which have only been seen in modern telecommunication until now.
Flow similarity model predicts the allometry and allometric covariation of petiole dimensions
Authors: Price Charles A.
Published: January 2023

Allometric relationships for plants, plant organs and plant parts, have long generated interest among biologists. Several prominent theoretical models based on biomechanical and/or hydraulic arguments, have been introduced with mixed support. Here I test a more recent offering, flow similarity, which is based on the conservation of volumetric flow rate and velocity. Using dimensional data for 935 petioles from 43 angiosperm species, I show that both the intraspecific and interspecific petiole allometries are more closely aligned with the predictions of the flow similarity model than that of elastic or geometric similarity. Further, allometric covariation among empirical scaling exponents falls along predicted functions with clustering around the flow similarity predictions. This work adds to the body of literature highlighting the importance of hydraulics in understanding the physiological basis of plant allometries, identifies previously unknown central tendencies in petiole allometry, and helps to delineate the scope within which the flow similarity model may be applicable.
Leveraging family data to design Mendelian Randomization that is provably robust to population stratification
Authors: LaPierre Nathan , Fu Boyang , Turnbull Steven , Eskin Eleazar , Sankararaman Sriram
Published: January 2023

Mendelian Randomization (MR) has emerged as a powerful approach to leverage genetic instruments to infer causality between pairs of traits in observational studies. However, the results of such studies are susceptible to biases due to weak instruments as well as the confounding effects of population stratification and horizontal pleiotropy. Here, we show that family data can be leveraged to design MR tests that are provably robust to confounding from population stratification, assortative mating, and dynastic effects. We demonstrate in simulations that our approach, MR-Twin, is robust to confounding from population stratification and is not affected by weak instrument bias, while standard MR methods yield inflated false positive rates. We applied MR-Twin to 121 trait pairs in the UK Biobank dataset and found that MR-Twin identifies likely causal trait pairs and does not identify trait pairs that are unlikely to be causal. Our results suggest that confounding from population stratification can lead to false positives for existing MR methods, while MR-Twin is immune to this type of confounding.
The probability of edge existence due to node degree: a baseline for network-based predictions
Authors: Zietz Michael , Himmelstein Daniel S. , Kloster Kyle , Williams Christopher , Nagle Michael W. , Greene Casey S.
Published: January 2023

Important tasks in biomedical discovery such as predicting gene functions, gene-disease associations, and drug repurposing opportunities are often framed as network edge prediction. The number of edges connecting to a node, termed degree, can vary greatly across nodes in real biomedical networks, and the distribution of degrees varies between networks. If degree strongly influences edge prediction, then imbalance or bias in the distribution of degrees could lead to nonspecific or misleading predictions. We introduce a network permutation framework to quantify the effects of node degree on edge prediction. Our framework decomposes performance into the proportions attributable to degree and the network’s specific connections. We discover that performance attributable to factors other than degree is often only a small portion of overall performance. Degree’s predictive performance diminishes when the networks used for training and testing—despite measuring the same biological relationships—were generated using distinct techniques and hence have large differences in degree distribution. We introduce the permutation-derived edge prior as the probability that an edge exists based only on degree. The edge prior shows excellent discrimination and calibration for 20 biomedical networks (16 bipartite, 3 undirected, 1 directed), with AUROCs frequently exceeding 0.85. Researchers seeking to predict new or missing edges in biological networks should use the edge prior as a baseline to identify the fraction of performance that is nonspecific because of degree. We released our methods as an open-source Python package (https://github.com/hetio/xswap/).
An entorhinal-like region in food-caching birds
Authors: Applegate Marissa C. , Gutnichenko Konstantin S. , Mackevicius Emily L. , Aronov Dmitriy
Published: January 2023

The mammalian entorhinal cortex routes inputs from diverse sources into the hippocampus. This information is mixed and expressed in the activity of many specialized entorhinal cell types, which are considered indispensable for hippocampal function. However, functionally similar hippocampi exist even in non-mammals that lack an obvious entorhinal cortex, or generally any layered cortex. To address this dilemma, we mapped extrinsic hippocampal connections in chickadees, whose hippocampi are used for remembering numerous food caches. We found a well-delineated structure in these birds that is topologically similar to the entorhinal cortex and interfaces between the hippocampus and other pallial regions. Recordings of this structure revealed entorhinal-like activity, including border and multi-field grid-like cells. These cells were localized to the subregion predicted by anatomical mapping to match the dorsomedial entorhinal cortex. Our findings uncover an anatomical and physiological equivalence of vastly different brains, suggesting a fundamental nature of entorhinal-like computations for hippocampal function.
The Field-Dependent Nature of PageRank Values in Citation Networks
Authors: Heil Benjamin J. , Greene Casey S.
Published: January 2023

The value of scientific research can be easier to assess at the collective level than at the level of individual contributions. Several journal-level and article-level metrics aim to measure the importance of journals or individual manuscripts. However, many are citation-based and citation practices vary between fields. To account for these differences, scientists have devised normalization schemes to make metrics more comparable across fields. We use PageRank as an example metric and examine the extent to which field-specific citation norms drive estimated importance differences. In doing so, we recapitulate differences in journal and article PageRanks between fields. We also find that manuscripts shared between fields have different PageRanks depending on which field’s citation network the metric is calculated in. We implement a degree-preserving graph shuffling algorithm to generate a null distribution of similar networks and find differences more likely attributed to field-specific preferences than citation norms. Our results suggest that while differences exist between fields’ metric distributions, applying metrics in a field-aware manner rather than using normalized global metrics avoids losing important information about article preferences. They also imply that assigning a single importance value to a manuscript may not be a useful construct, as the importance of each manuscript varies by the reader’s field.
Are We Seeing the Unseen of Human Trafficking? A Retrospective Secondary Analysis of the CTDC K-Anonymized Global Victim of Trafficking Data Pool in the Period 2010-2020
Authors: Al-Tammemi Ala’a B. , Nadeem Asma , Kutkut Laila , Ali Manal , Angawi Khadijah , Abdallah Maram H. , Abutaima Rana , Shoumar Rasha , Albakri Rana , Sallam Malik
Published: January 2023

Background

Human trafficking is considered a hidden global threat with unsubstantiated numbers despite the estimation of the presence of around 40.3 million victims worldwide. Human trafficking results in severe detrimental impacts on both mental and physical health. Given the sensitivity and negative consequences of human trafficking on the global system and victims, and considering the scarce research in this area, our current study aimed at describing the (i) Sociodemographic profiles of anonymized victims, (ii) Means of control, and (iii) Purpose of trafficking, utilizing the largest anonymized and publicly available dataset on victims of human trafficking.

Methods

This is a retrospective secondary analysis of the Counter-Trafficking Data Collaborative (CTDC) data pool in the period from 2010 to 2020. The utilized dataset is called the k-anonymized global victim of trafficking dataset, and it is considered the largest global dataset on victims of human trafficking. Data from the k-anonymized data pool were extracted and exported to Statistical Package for Social Sciences, SPSS® version 27.0 for Windows (IBM Corp. Version 27.0.Armonk, NY) for quality check and analysis using descriptive statistics.

Results

A total of 87003 victims of human trafficking were identified in the period from 2010 to 2020. The most age category encountered among victims was 9-17 years with around 10326 victims (11.9%), followed by 30-38 years with 8562 victims (9.8%). Females comprised 70% of the sample with 60938 victims. The United States (n=51611), Russia (n=4570), and the Philippines (n=1988) comprised the most countries of exploitation/trafficking. Additionally, the year 2019 witnessed the greatest number of victims registered for assistance by anti-trafficking agencies with around 21312 victims (24.5%). Concerning means of control, threats, psychological abuse, restriction of the victim’s movement, taking the victim’s earnings, and physical abuse were the most reported means. Around 42685 victims (49.1%) reported sexual exploitation as the purpose of their trafficking, followed by forced labor with 18176 victims (20.9%).

Conclusion

Various means and methods can be used by traffickers to control the victims to be trafficked for many purposes, with sexual exploitation and forced labor being the most common ones. Global anti-trafficking efforts should be brought together in solidarity through utilizing the paradigm of protection of victims, prosecution of traffickers, prevention of trafficking, and inter-sectoral partnerships. Despite being a global concern with various reports that tried to capture the number of trafficked victims worldwide, human trafficking still has many unseen aspects that impose a significant challenge and adds to the global burden in combatting this threat.
Assessment of distant-site rescue elements for CRISPR toxin-antidote gene drives
Authors: Chen Jingheng , Xu Xuejiao , Champer Jackson
Published: January 2023

New types of gene drives promise to provide increased flexibility, offering many options for confined modification or suppression of target populations. Among the most promising are CRISPR toxin-antidote gene drives, which disrupt essential wild-type genes by targeting them with Cas9/gRNA, resulting in their removal. This increases the frequency of the drive in the population. All these drives, plus homing modification rescue drives, rely on having an effective rescue element, which consists of a recoded version of the target gene. This rescue element can be at the same site as the target gene, which maximizes the chance of efficient rescue, or at a distant site, which allows some other useful options, such as easily disrupting another essential gene or achieving greater confinement. Previously, we developed a homing rescue drive targeting a haplolethal gene and a toxin-antidote drive targeting an essential but haplosufficient gene. These successful drives had functional rescue elements but suboptimal drive efficiency. Here, we attempted to construct new toxin-antidote drives targeting these genes with a distantsite configuration from three different loci. We found that use of additional gRNAs increased cut rates to nearly 100%. However, all distant-site rescue elements failed for both haplolethal and haplosufficient target genes. Furthermore, one rescue element with a minimally recoded rescue element was used as a template for homology-directed repair for the target gene on a different chromosomal arm, resulting in the formation of functional resistance alleles at high frequency. Together, these results can inform the design of future CRISPR-based toxin-antidote gene drives.