bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges in the Long-term Management of Patients With Coccidioidal Meningitis: A Retrospective Analysis of Treatment and Outcomes
Authors: Sivasubramanian Geetha , Kadakia Saurin , Kim Jani M , Pervaiz Sarah , Yan Yueqi , Libke Robert
Published: May 2023

Background

Coccidioidal meningitis (CM) is the most severe form of disseminated coccidioidomycosis. Despite years of clinical experience, it remains a difficult condition to treat, often requiring surgical procedures, such as placement of a ventriculoperitoneal shunt, in addition to lifelong antifungal therapy.

Methods

We performed a retrospective analysis of patients with CM seen in a large referral center in Central Valley, California, from 2010 to 2020. Data pertinent to CM were collected and analyzed.

Results

Among 133 patients with CM identified in the 10-year period, nonadherence to antifungal therapy was noted in 43% of patients. Of the 80 patients who underwent ventriculoperitoneal shunt placement for management of intracranial pressure, shunt failure requiring revision surgery occurred in 42 (52.5%). Rehospitalizations due to CM-related reasons occurred in 78 of 133 patients (59%). Twenty-three percent of patients (n = 29) died due to complications from CM, on an average 22 months after the diagnosis of CM. Encephalopathy at presentation was associated with a significantly higher risk of death.

Conclusions

Patients with CM in central California are predominantly rural agricultural workers with elevated levels of poverty and low health literacy and many barriers to care, leading to high rates of medication nonadherence and loss to follow-up outpatient care. Management challenges are frequent, such as failure of antifungal therapy, high rates of rehospitalization, and the need for repeated shunt revision surgeries. In addition to the development of curative new antifungal agents, understanding the barriers to patient adherence to care and antifungal therapy and identifying means to overcome such barriers are of paramount importance.
Single‐cell RNA‐seq with spatial transcriptomics to create an atlas of human diabetic kidney disease
Authors: Chen Duo , Shao Mingwei , Song Yi , Ren Gaofei , Guo Feng , Fan Xunjie , Wang Yanyan , Zhang Wei , Qin Guijun
Published: May 2023

Diabetic kidney disease (DKD) develops in ~40% of patients with diabetes and is the leading cause of chronic kidney disease worldwide. We used single‐cell RNA‐sequencing and spatial transcriptomic analyses of kidney specimens from patients with DKD. Unsupervised clustering revealed distinct cell clusters, including epithelial cells and fibroblasts. We also identified differentially expressed genes (DEGs) and assessed enrichment, and cell–cell interactions. Specific enrichment of DKD was evident in venous endothelial cells (VECs) and fibroblasts with elevated CCL19 expression. The DEGs in most kidney parenchymal cells in DKD were primarily enriched in inflammatory signaling pathways. Intercellular crosstalk revealed that most cell interactions in DKD are associated with chemokines. Spatial transcriptomics revealed that VECs co‐localized with fibroblasts, with most immune cells being enriched in areas of renal fibrosis. These results provided insight into the cell populations, intercellular interactions, and signaling pathways underlying the pathogenesis and potential targets for treating DKD.
Bridge Plate Fixation of Distal Femur Fractures: Defining Deficient Radiographic Callus Formation and Its Associations
Authors: Crutcher William L. , Magnusson Erik A. , Griffith Kyle M. , Alford Cory A. , Nielsen Ena D. , Elkins Jacob M. , Lujan Trevor J. , Kleweno Conor P. , Lack William D.
Published: May 2023

Objective:

To determine whether deficient early callus formation can be defined objectively based on the association with an eventual nonunion and specific patient, injury, and treatment factors.

Methods:

Final healing outcomes were documented for 160 distal femur fractures treated with locked bridge plate fixation. Radiographic callus was measured on postoperative radiographs until union or nonunion had been declared by the treating surgeon. Deficient callus was defined at 6 and 12 weeks based on associations with eventual nonunion through receiver–operator characteristic analysis. A previously described computational model estimated fracture site motion based on the construct used. Univariable and multivariable analyses then examined the association of patient, injury, and treatment factors with deficient callus formation.

Results:

There were 26 nonunions. The medial callus area at 6 weeks <24.8 mm2 was associated with nonunion (12 of 39, 30.8%) versus (12 of 109, 11.0%), P = 0.010. This association strengthened at 12 weeks with medial callus area <44.2 mm2 more closely associated with nonunion (13 of 28, 46.4%) versus (11 of 120, 9.2%), P <0.001. Multivariable logistic regression analysis found limited initial longitudinal motion (OR 2.713 (1.12–6.60), P = 0.028)) and Charlson Comorbidity Index (1.362 (1.11–1.67), P = 0.003) were independently associated with deficient callus at 12 weeks. Open fracture, mechanism of injury, smoking, diabetes, plate material, bridge span, and shear were not significantly associated with deficient callus.

Conclusion:

Deficient callus at 6 and 12 weeks is associated with eventual nonunion, and such assessments may aid future research into distal femur fracture healing. Deficient callus formation was independently associated with limited initial longitudinal fracture site motion derived through computational modeling of the surgical construct but not more routinely discussed parameters such as plate material and bridge span. Given this, improved methods of in vivo assessment of fracture site motion are necessary to further our ability to optimize the mechanical environment for healing.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
An Asymptomatic Case of Invisible Mycosis Fungoides
Authors: Peters Kristopher , Onajin Oluwakemi , Ruiz de Luzuriaga Arlene , Lullo Jenna , Shea Christopher R.
Published: May 2023

Mycosis fungoides has previously been reported in ‘invisible’ form, when biopsy of normal-appearing skin in the background of undifferentiated chronic pruritus demonstrated histopathologic findings of the malignancy. Asymptomatic cases have been reported more infrequently on biopsies of individual skin lesions. We present a case of invisible and asymptomatic mycosis fungoides, confirmed with immunohistochemical and T-cell receptor gene rearrangement studies, diagnosed on a re-excision specimen of an atypical melanocytic nevus. The case highlights the importance of alert examination of all tissue specimens for evidence of unrelated pathologic findings.
Comparative Immunohistochemical Analysis of Macrophage Phenotypes in Cutaneous Sarcoid Granuloma, Suture Granuloma, and Lipogranuloma
Authors: Nakamura Toshitsugu , Fujiwara Masayuki
Published: May 2023

Granulomas are composed of a heterogeneous population of resident and recruited macrophages according to the type of lesion, extent of injury, and local tissue environment (eg, involved site and interaction with infiltrating lymphocytes). Although macrophage phenotypes in various types of granulomas have been previously described, the experimental conditions varied across studies, precluding a comparative and comprehensive understanding of granulomas. This study was conducted to comparatively analyze the expression of markers of the M1 and M2 phenotypes in macrophages that compose various types of granulomas, including epithelioid lesions, under strict conditions. Surgical specimens of cutaneous sarcoidosis (11 lesions), suture granuloma (10 lesions), and subcutaneous lipogranuloma (12 lesions) were immunohistochemically stained for CD11c, CD206, CD163, and CD10. The expression of these markers in macrophages composing each type of granuloma was scored and statistically analyzed. Granuloma macrophages were mostly immunoreactive for CD11c and CD206 in all the examined cases, although many intermingling CD206-negative cells were observed in 5 cases of lipogranuloma. CD163 and CD10 were diffusely expressed in macrophages composing suture granuloma and lipogranuloma, whereas they were not expressed in epithelioid cells in cutaneous sarcoidosis. Meanwhile, “interstitial” macrophages around epithelioid granulomas revealed moderate to marked CD163 expression in 7 lesions of cutaneous sarcoidosis. These results indicate significant differences of expression of CD163 and CD10 between cutaneous sarcoidosis and suture granuloma/lipogranuloma; CD163 and CD10 are downregulated after the epithelioid transformation of macrophages in cutaneous sarcoidosis.
Cutaneous Malignant Melanoma With Rhabdomyosarcomatous Dedifferentiation: an Immunohistological and Molecular Case Study With Literature Review
Authors: O'Neill Paul , Amanuel Benhur , Mesbah Ardakani Nima
Published: May 2023

Cutaneous malignant melanoma can show a wide range of cytomorphological variability, in particular exhibiting a rhabdoid appearance is not uncommon in melanoma cells; however, the phenomenon of “dedifferentiation” with loss of melanocytic immunohistochemical properties and expression of skeletal muscle immunomarkers is exceedingly rare. Owing to the rarity of such melanomas, their clinicopathological features and molecular profile remain largely unknown. In this report, we describe the clinical, immunomorphological, and molecular features of melanomas with rhabdomyosarcomatous dedifferentiation by presenting a new case and exploring the literature for the previously reported cases.
Effect of Anesthesia Duration on Intravitreal Injection Pain：A Double-blinded Randomized Comparative Study
Authors: Ma Xiubin , Liang Qianqian , Xue Shuyue , Ren Qi , Du Qing , Zhang Zhichun , Li Xinying , Liu Xin , Gao Yan , Li Jun
Published: May 2023

Purpose:

To determine the effect of different durations of topical anesthesia on intravitreal injection (IVI) pain.

Methods:

This was a double-blinded randomized comparative study. Three hundred and twelve sequential eyes undergoing IVI were randomized to one of six groups according to the duration of topical anesthesia (from 1 to 30 minutes, one group for every 5-minute range, Group 1–6). Topical anesthesia before IVI was standardized. Patients graded their pain using the visual analogue scale (VAS) and the Wong-Baker FACES Scale (WBF) at 15 minutes after the procedure.

Results:

The pain scores among the six groups were significantly different for the VAS (P = 0.013) and WBF (P = 0.024). The mean pain scores for Group 4 were 1.97 ± 1.04 (VAS) and 2.02 ± 1.08 (WBF) and were significantly lower than those of Group 1, 2, 5, or 6.

Conclusion:

The duration of topical anesthesia was significantly correlated with IVI pain. Preoperative 0.5% proparacaine hydrochloride drops were most effective in relieving IVI pain 11–20 minutes after topical administration.
Can ChatGPT Accurately Answer a PICOT Question? Assessing AI Response to a Clinical Question
Authors: Branum Candise , Schiavenato Martin
Published: May 2023

Background:

ChatGPT, an artificial intelligence (AI) text generator trained to predict correct words, can provide answers to questions but has shown mixed results in answering medical questions.

Purpose:

To assess the reliability and accuracy of ChatGPT in providing answers to a complex clinical question.

Methods:

A Population, Intervention, Comparison, Outcome, and Time (PICOT) formatted question was queried, along with a request for references. Full-text articles were reviewed to verify the accuracy of the evidence summary provided by the chatbot.

Results:

ChatGPT was unable to provide a certifiable response to a PICOT question. The references cited as evidence included incorrect journal information, and many study details summarized by ChatGPT proved to be patently false, including providing fabricated data.

Conclusions:

ChatGPT provides answers that appear legitimate but may be factually incorrect. The system is not transparent in how it gathers data to answer questions and sometimes fabricates information that looks plausible, making it an unreliable tool for clinical questions.
Increasing Diversity in the Advanced Practice Nursing Workforce Through Partnerships With Historically Black Colleges
Authors: Johnson Ragan , Lyons-Smith Marquita , Derouin Anne , Carter Brigit , VanRiel Yolanda
Published: May 2023

Background:

Health inequities have enhanced efforts to diversify the nursing workforce. Despite recruitment strategies, the percentage of Black nurse practitioners (NPs) lags in comparison with the populous.

Problem:

Barriers to improving workforce diversity can be traced to academic nursing’s lack of diversity in faculty, under-resourced education opportunities for students from underrepresented backgrounds, and historical hurdles.

Approach:

One systems-level approach to increasing NP workforce diversity is developing pathway programs aimed at preparing, recruiting, and supporting Black students into advanced practice nursing education. Current undergraduate RN students from 2 historically Black colleges and universities (HBCUs) attended a 1-week summer immersion program at a graduate school of nursing at a predominately White institution.

Conclusion:

Pathway programs for Black undergraduate RN students show promise for increasing awareness of graduate nursing, offering race and ethnicity concordant mentorship, and cultivating deep awareness for health equity.
Development of Kaptive databases for Vibrio parahaemolyticus O- and K-antigen genotyping
Authors: van der Graaf-van Bloois Linda , Chen Hongyou , Wagenaar Jaap A. , Zomer Aldert L.
Published: May 2023

Vibrio parahaemolyticus

is an important food-borne human pathogen and presents immunogenic surface polysaccharides, which can be used to distinguish problematic and disease-causing lineages.

V. parahaemolyticus

is divided in 16 O-serotypes (O-antigen) and 71 K-serotypes (K-antigen). Agglutination tests are still the gold standard for serotyping, but many

V. parahaemolyticus

isolates are not typable by agglutination. An alternative for agglutination tests is genotyping using whole-genome sequencing data, by which K- and O- genotypes have been curated and identified previously for other clinically relevant organisms with the software tool Kaptive. In this study,

V. parahaemolyticus

isolates were serotyped and sequenced, and all known and several novel O- and K-loci were identified. We developed Kaptive databases for all O- and K-loci after manual curation of the loci. In our study, we could genotype the O- and K-loci of 98 and 93 % of the genomes, respectively, with a Kaptive confidence score higher than ‘none’. The newly developed Kaptive databases with the identified

V. parahaemolyticus

O- and K-loci can be used to identify the O- and K-genotypes of

V. parahaemolyticus

isolates from genome sequences.
QUEST-AI: A System for Question Generation, Verification, and Refinement using AI for USMLE-Style Exams
Authors: Bedi Suhana , Fleming Scott L. , Chiang Chia-Chun , Morse Keith , Kumar Aswathi , Patel Birju , Jindal Jenelle A. , Davenport Conor , Yamaguchi Craig , Shah Nigam H.
Published: May 2023

The United States Medical Licensing Examination (USMLE) is a critical step in assessing the competence of future physicians, yet the process of creating exam questions and study materials is both time-consuming and costly. While Large Language Models (LLMs), such as OpenAI’s GPT-4, have demonstrated proficiency in answering medical exam questions, their potential in generating such questions remains underexplored. This study presents QUEST-AI, a novel system that utilizes LLMs to (1) generate USMLE-style questions, (2) identify and flag incorrect questions, and (3) correct errors in the flagged questions. We evaluated this system’s output by constructing a test set of 50 LLM-generated questions mixed with 50 human-generated questions and conducting a two-part assessment with three physicians and two medical students. The assessors attempted to distinguish between LLM and human-generated questions and evaluated the validity of the LLM-generated content. A majority of exam questions generated by QUEST-AI were deemed valid by a panel of three clinicians, with strong correlations between performance on LLM-generated and human-generated questions. This pioneering application of LLMs in medical education could significantly increase the ease and efficiency of developing USMLE-style medical exam content, offering a cost-effective and accessible alternative for exam preparation.
Spatial clusters and social inequities in Covid-19 vaccine coverage among children in Brazil
Authors: Boing Alexandra Crispim , Boing Antonio Fernando , Borges Marcelo Eduardo , Rodrigues Denis de Oliveira , Barberia Lorena , Subramanian SV
Published: May 2023

This study examined the spatial distribution and social inequalities in COVID-19 vaccine coverage among children aged 5-11 in Brazil. First and second dose vaccine coverage was calculated for all Brazilian municipalities and analyzed by geographic region and deciles based on human development index (HDI-M) and expected years of schooling at 18 years of age. Multilevel models were used to determine the variance partition coefficient, and bivariate local Moran`s I statistic was used to assess spatial association. Results showed significant differences in vaccine coverage rates among Brazilian municipalities, with lower coverage in the North and Midwest regions. Municipalities with lower HDI and expected years of schooling had consistently lower vaccine coverage rates. Bivariate clustering analysis identified extensive concentrations of municipalities in the Northern and Northeastern regions with low vaccine coverage and low human development, while some clusters of municipalities in the Southeast and South regions with low coverage were located in areas with high HDI-M. These findings highlight the persistent municipal-level inequalities in vaccine coverage among children in Brazil and the need for targeted interventions to improve vaccine access and coverage in underserved areas.
A double-blind trial of decoded neurofeedback intervention for specific phobias
Authors: Cushing Cody A. , Lau Hakwan , Kawato Mitsuo , Craske Michelle G. , Taschereau-Dumouchel Vincent
Published: May 2023

Aim

A new closed-loop fMRI method called multi-voxel neuro-reinforcement has the potential to alleviate the subjective aversiveness of exposure-based interventions by directly inducing phobic representations in the brain, outside of conscious awareness. The current study seeks to test this method as an intervention for specific phobia.

Methods

In a randomized, double-blind, controlled single-university trial, individuals diagnosed with at least two (1 target, 1 control) animal subtype specific phobias were randomly assigned (1:1:1) to receive 1, 3, or 5 sessions of multi-voxel neuro-reinforcement in which they were rewarded for implicit activation of a target animal representation. Amygdala response to phobic stimuli was assessed by study staff blind to target and control animal assignments. Pre-treatment to post-treatment differences were analyzed with a 2-way repeated-measures ANOVA.

Results

A total of 23 participants (69.6% female) were randomized to receive 1 (n=8), 3 (n=7), or 5 (n=7) sessions of multi-voxel neuro-reinforcement. Eighteen (n=6 each group) participants were analyzed for our primary outcome. After neuro-reinforcement, we observed an interaction indicating a significant decrease in amygdala response for the target phobia but not the control phobia. No adverse events or dropouts were reported as a result of the intervention.

Conclusion

Results suggest multi-voxel neuro-reinforcement can specifically reduce threat signatures in specific phobia. Consequently, this intervention may complement conventional psychotherapy approaches with a non-distressing experience for patients seeking treatment. This trial sets the stage for a larger randomized clinical trial to replicate these results and examine the effects on real-life exposure.

Clinical Trial Registration

The now-closed trial was prospectively registered atClinicalTrials.govwith IDNCT03655262.
Improving capacity for advanced training in obstetric surgery: Evaluation of a blended learning approach
Authors: Allott Helen , Smith Alan , White Sarah , Nyaoke Irene , Evans Ogoti , Oduor Michael Oriwo , Karangau Steven , Sawe Sheila , Shaaban Nassir , Ephraim Ochola , Ameh Charles Anawo
Published: May 2023

Introduction

Significant differences in outcomes for mothers and babies following obstetric surgical interventions between low- and middle-income countries and high-income settings have demonstrated a need for improvements in quality of care and training of obstetric surgical and anaesthetic providers. To address this a five-day face-to-face training intervention was developed. When the COVID-19 pandemic interrupted its roll-out, the course was redesigned for delivery by blended learning.

Methods

This 3-part blended-learning course (part-1: 15 hours self-directed online learning, part-2: 13 hours facilitated virtual workshops and part-3: 10 hours face-to-face delivery), was conducted in Kenya. We assessed the completion rate of part-1 (21 assignments), participation rate in parts 2 and 3, participant satisfaction, change in knowledge and skills and compared the cost of the blended delivery compared to the 5-day face-to-face delivery, in GB Pounds.

Results

65 doctors took part in part 1, 53 completing at least 90% of the assignments. 60 doctors participated in part 2, and 53 participated in part 3. Participants completing an evaluation reported (n=53) attending the training was a good use of their time (each of parts-1 and 3: 98%, part-2: 94%) and would recommend this to other colleagues (part-1 and 3: 98%, part-2: 90%). Mean (SD) knowledge score improved from 64% (7%) to 80% (8%) and practical skills from 44% (14%) to 87% (7%). The blended course achieved a cost-saving of £207 per participant compared to the 5-day face-to-face delivery approach.

Conclusion

We have demonstrated that a blended learning approach to clinical training in a low resource setting is feasible, acceptable and more cost effective. More studies are required to investigate the effectiveness of this approach on health outcomes.
Validation of a Visual Midline Gauge: A Cross-Sectional Study
Authors: Stalin Amritha , Ding Ran , J. Leat Susan , Binhilabi Ohwod , Labreche Tammy
Published: May 2023

Background

This study standardized the parameters of a novel visual midline gauge and presents normative data, which can be used by optometrists in the assessment of visual midline.

Methods

Ninety-three participants from three age groups (18 to 44, 45 to 64, and > 65 years) without history of significant neurological or ocular problems were recruited in Waterloo, Canada and Hong Kong. In experiment 1, the perceived horizontal and vertical visual midline was measured using the gauge for 2 speeds and 2 repositioning methods. In experiment 2, the perceived midline was measured for three different distances (25, 50 and 100 cm) using a target speed and repositioning method chosen from the first experiment results. Since there was no significant difference between the two sites in any of the measures, data were combined for analysis.

Results

For experiment 1, linear mixed models showed no effect of age, speed or repositioning method and no interaction (p>0.05) for the perceived midline position (p>0.05). In experiment 2, there was no significant effect of age or distance and no interaction effects on the perceived horizontal and vertical visual midline position using the chosen speed and method (2.3 degrees per second, adjustment method). Normative data (mean and 95% ranges of the perceived visual midline for control participants) was tabulated. The measurements were found to be repeatable. A few participants were found to have significant midline shifts.

Conclusion

This study shows that the measurement of midline is tolerant of differences of target speed, testing method, test distance, and age group of the participants and that the measurements using the visual midline gauge are repeatable. It is possible for even individuals without a history of neurological or ocular disorders to have significant shifts in their perceived visual midline.
Payments to healthcare organisations reported by the medical device industry in Europe from 2017 to 2019: an observational study
Authors: Larkin James , Mulinari Shai , Ozieranski Piotr , Lynch Kevin , Fahey Tom , Ozaki Akihiko , Moriarty Frank
Published: May 2023

Background

Medical device industry payments to healthcare organisations (HCOs) can create conflicts of interest which can undermine patient care. One way of addressing this concern is by enhancing transparency of industry financial support to HCOs. MedTech Europe, a medical device trade body, operate a system of disclosure of education payments to European HCOs. This study aimed to characterise payments reported in this database and to evaluate the disclosure system.

Methods

An observational study of education-related payments to HCOs reported by the medical device industry in Europe was conducted. Data was manually extracted from transparentmedtech.eu. The primary outcome variable is the value of the payments, overall, and for each year, payment type, and country. The accessibility, availability and quality of the database was also analysed, using a proforma with 15 measures.

Findings

Overall, 116 medical device companies reported education-related payments in 53 countries, valuing over €420 million between 2017-2019, increasing in value between 2017-2019, from €91,289,672 to €175,414,302. Ten countries accounted for 94% of all payments and ten companies accounted for 80% of all payments. The accessibility, availability and quality of the database, rated low for six measures, medium for six measures and high for three measures.

Interpretation

There is a large amount of education-related payments from medical device companies to European HCOs, creating substantial potential for conflicts of interest. MedTech Europe’s disclosure system has many shortcomings. A European-wide publicly mandated disclosure system for both the medical device and pharmaceutical industries should be introduced.

Funding

Swedish Research Council (SM, PO)
Genetic characterization of the ALFA study: Uncovering genetic profiles in the Alzheimer’scontinuum
Authors: Vilor-Tejedor Natalia , Genius Patricia , Rodríguez-Fernández Blanca , Minguillón Carolina , Sadeghi Iman , González-Escalante Armand , Crous-Bou Marta , Suárez-Calvet Marc , Grau-Rivera Oriol , Brugulat-Serrat Anna , Sanchez-Benavides Gonzalo , Esteller Manel , Fauria Karine , Molinuevo José Luis , Navarro Arcadi , Gispert Juan Domingo ,   the Alzheimer’s Disease Neuroimaging Initiative,   the ALFA study
Published: May 2023

In 2013, the ALFA (ALzheimer and FAmilies) project was established to investigate pathophysiological changes in preclinical Alzheimer’s disease (AD), and to foster research on early detection and preventive interventions. Since then, it has prospectively followed cognitively unimpaired late/middle-aged participants, most of whom are adult children of AD patients. Risk stratification of cognitively unimpaired individuals, including genetic factors is key for implementing AD prevention strategies. Here, we report the genetic characterization of ALFA participants with respect to neurodegenerative/cerebrovascular diseases, AD biomarkers, brain endophenotypes, risk factors and aging biomarkers, emphasizing amyloid/tau status and gender differences. We additionally compared AD risk in ALFA to that across the full disease spectrum from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Results show that the ALFA project has been successful at establishing a cohort of cognitively unimpaired individuals at high genetic risk of AD. It is, therefore, well-suited to study early pathophysiological changes in the preclinical ADcontinuum.

Highlights

Prevalence of ε4 carriers in ALFA is higher than in the general European population.

The ALFA study is highly enriched in AD genetic risk factors beyondAPOE.

AD genetic profiles in ALFA are similar to clinical groups along thecontinuum.

ALFA has succeeded in establishing a cohort of CU individuals at high genetic AD risk.

ALFA is well suited to study pathogenic events/early pathophysiological changes in AD.
Prediction of future chronic hypertension from maternal characteristics in early pregnancy
Authors: Charakida Marietta , Wright Alan , Magee Laura A , Syngelaki Argyro , von Dadelszen Peter , Akolekar Ranjit , Wright David , Nicolaides Kypros H
Published: May 2023

Background

Pre-eclampsia (PE) and gestational hypertension (GH) identify women at increased risk of chronic hypertension (CH) and cardiovascular disease, but as efforts to prevent PE and GH advance, fewer women at increased cardiovascular risk will be identified.

Methods

Cohort of 26,511 women seen in two consecutive pregnancies. Included were women without CH, with information on maternal characteristics and blood pressure (BP) at 11-13 weeks’ gestation, and development of PE or GH in the index pregnancy. Logistic regression models were fitted for prediction of development of future CH by the 20thweek of the subsequent pregnancy. Performance of screening and risk calibration of the model were assessed.

Results

1560 (5.9%) women developed PE or GH (index pregnancy), and 215 (0.8%) developed future CH, a median of 3.0 years later. Predictors from the index pregnancy of development of future CH were: early pregnancy maternal age, weight and BP; Black or South Asian ethnicity; family history of PE; parity; and development of PE or GH. PE or GH accounted for 52.1% (95% confidence interval 45.2-58.9%) of future CH. At a screen-positive-rate of 10%, a model including terms for maternal characteristics and early pregnancy BP accounted for 67.9% (61.2-74.5) of future CH; addition of the development of PE or GH detected 73.5% (67.1-79.3) of future CH. Risks produced from the predictive model were well-calibrated and confirmed by five-fold cross-validation.

Conclusion

Early maternal characteristics and BP are effective in predicting development of future CH. As new interventions are expected to reduce the occurrence of PE and GH, our study results offer an alternative strategy for identifying women at increased risk of future CH and are applicable worldwide.
Zika Virus looming epidemic in Pakistan: seroprevalence findings by plaque reduction neutralization test in the Sindh Region of Pakistan
Authors: Imtiaz Khekashan , Farooqi Joveria , Barr Kelli L. , Kanji Akbar , Prakoso Dhani , Azizullah Zahida , Long Maureen T. , Khan Erum
Published: May 2023

Background

Zika virus (ZIKV) has emerged as a cause of febrile illness in children and adults globally. West Asian and Middle Eastern countries have not yet experienced the widespread emergence of ZIKV. In Pakistan, detection of ZIKV antibodies have been reported. However, the validity of this data is questionable given the current understanding of flaviviral antigenic cross-reactivity. In order to determine if ZIKV is circulating in the Sindh region of Pakistan, patients presenting to healthcare centers with an acute febrile dengue-like illness were evaluated for ZIKV infection.

Methods

Dengue virus (DENV) screening in patients was performed using a commercial ELISA Rapid Test NS1 antigen capture test. All DENV negative samples were tested for Zika virus, using a commercial IgM capture ELISA kit. Additionally, a plaque reduction neutralization test (PRNT) was performed to measure neutralizing antibodies. Singleplex, two-step Real-time PCR using general primers and probes was performed for the detection of Zika virus nucleic acid.

Results

Patients with acute dengue-like illness (DLI) presenting at healthcare centers in different sites throughout the Sindh region of Pakistan were recruited. A total of 745 patient samples were tested for ZIKV via IgM ELISA and RT-PCR. Thirty-seven samples (4.9%) tested positive for ZIKV IgM without any cross-reactivity to other flaviviruses tested simultaneously. These were considered as presumptive positive for ZIKV, selected presumptive positive samples (n=20) were confirmed using PRNT50 using Vero cells. All 20 samples showed ZIKV neutralization at PRNT50.

Conclusions

Our study provides evidence that ZIKV is circulating in the Sindh region of Pakistan and is a probable cause of clinical dengue-like illness (DLI) cases that are seen seasonally in Pakistan.
Deep brain stimulation in globus pallidus internus travels to thalamus and subthalamic nuclei along physiological pathways
Authors: Kasiri Maral , Vidmark Jessica , Hernandez-Martin Estefania , Mousavi S. Alireza Seyyed , Sanger Terence D.
Published: May 2023

Deep brain stimulation (DBS) is a neuromodulation method for treatment of various neurological disorders. It is often assumed that the primary inhibition or excitation effect of DBS occurs at the site of stimulation. However, recent work has shown that DBS can lead to robust evoked potentials (EP) not only at the stimulation site, representing the local effect, but also in distant brain regions, representing the effects on distant targets. While the significance of these EPs for therapeutic outcomes is not known, it appears that the electrical effects of DBS have a partial modulatory impact on downstream targets. Nonetheless, it remains unclear through what mechanism DBS pulses travel to the distant targets or what portion of the pulses travel along the normal pathways from the stimulation site. The possible scenarios include orthodromic or antidromic pathways, accessory pathways, normally inhibited pathways, and direct electromagnetic activation of distant sites. The ability to record signals from brain regions provides an opportunity to determine the mechanism of DBS signal transmission. We hypothesize that the pathways that transmit DBS pulses include the pathways that transmit intrinsic neural signals. To test this, we performed a transfer function analysis on deep brain recordings during DBS-off condition and compared its impulse response with the transmission of signals from electrical stimulation during DBS-on condition. Our results support our claim that the electrical pulses travel partly along intrinsic neural pathways by showing that the propagation of DBS signals can be partially predicted by observation of intrinsic neural activity and measurement of DBS-EPs.

New & noteworthy

This study enhances the understanding of deep brain stimulation (DBS) mechanism by exploring how electrical stimulation travels along neural pathways. We utilized a computational method to explain the main routes through which DBS pulses travel. Our results suggest that DBS signals are likely to be transmitted along the normal pathways. This provides a basis to develop complex and nonlinear models of brain and relate the modulatory effect of stimulation to the brain connectome.
Closing the accessibility gap to mental health treatment with a conversational AI-enabled self-referral tool
Authors: Habicht Johanna , Viswanathan Sruthi , Carrington Ben , Hauser Tobias , Harper Ross , Rollwage Max
Published: May 2023

Accessing mental health care can be challenging, and minority groups often face additional barriers. This study investigates whether digital tools can enhance equality of access to mental health treatment. We evaluated a novel AI-enabled self-referral tool (a chatbot) designed to make entry to mental health treatment more accessible in a real-world setting.

In a multi-site observational study, data were collected from 129,400 patients who referred to 28 separate NHS Talking Therapies services across England. Our results indicate that the tool led to a 15% increase in total referrals, which was significantly larger than the 6% baseline increase observed in matched services using traditional self-referral methods during the same time period. Importantly, the tool was particularly effective for minority groups, which included non-binary (235% increase), bisexual (30% increase), and ethnic minority individuals (31% increase). This paints a promising picture for the use of AI chatbots in mental healthcare and suggests they may be especially beneficial for demographic groups that experience barriers to accessing treatment in the traditional care systems.

To better understand the reasons for this disproportional benefit for minority groups, we used thematic analysis and Natural Language Processing (NLP) models to evaluate qualitative feedback from 42,332 individuals who referred through the AI-enabled tool. We found that the tool’s human-free nature and its ability to improve the perceived need for treatment were the main drivers for improved diversity.

These findings suggest that AI-enabled chatbots have the potential to increase accessibility to mental health services for all, and to alleviate barriers faced by disadvantaged populations. The results have important implications for healthcare policy, clinical practice, and technology development.
Extraction and Reduction of the Parameters of Archimedes Spirals Drawn by Patients
Authors: Khan Furrukh , Xiaoxi Jessie , Dalm Brian , Thomas Evan
Published: May 2023

Analysis of patient’s hand drawn Archimedes spirals is commonly used in the medical community to grade various forms of tremors. These spirals are often drawn on paper using a pen or a pencil and then Xeroxed/scanned to turn the drawings into computer images. This process introduces artifacts such as misalignment of the paper, finite/variable width of the drawn line, light grey marks left by the toner, and greyscale background pixels introduced by the Xeroxing/scanning steps. Even a spiral drawn directly on the screen of a tablet produces lines with multi-pixel widths and varying greyscale values. These artifacts make it difficult to use image processing techniques to automatically extract the patient’s spiral as a clean single-valued discrete signal which could be treated mathematically for further analysis. We present a procedure in this paper to extract the patient’s hand-drawn spiral automatically as a mathematical discrete signal even in the presence of artifacts, with minimal user intervention. We also note that the spirals used by some hospitals and clinics are distorted and not perfect Archimedes spirals; nevertheless, our procedure can still be used for these cases. The extracted discrete signal is composed of a couple of thousand samples (features). The largeness of this feature space compared with the typical number of spiral samples at our disposal (of the order of only hundreds) makes it infeasible to apply Machine Learning techniques for predictions which generalize well in the real world without overfitting. We analyze the extracted discrete signal using FFT (Fast Fourier Transforms) and show that in FFT space the signal can be represented by as few as 300 parameters. The paper concludes that if these 300 parameters (or even 150 parameters for some problems) are used as a feature set for Machine Learning then it could very well be possible to make predictions which generalize well to the real world without overfitting. As a note, applications to actual Machine Learning problems are not covered in this paper.
Comparing the risks of diabetes, psychological distress, and radiation-induced cancer exposure after the Fukushima disaster using the loss of happy life expectancy
Authors: Murakami Michio , Ozaki Akihiko , Ono Kyoko , Nomura Shuhei , Takebayashi Yoshitake , Tsubokura Masaharu
Published: May 2023

After disasters, direct deaths and secondary health effects, such as diabetes and psychological distress, can occur. It is critical to compare the magnitudes of these risks to promote effective public health measures. In this study, we used the loss of happy life expectancy (LHpLE) to compare the risks associated with diabetes, psychological distress, and radiation-induced cancer after the 2011 Fukushima disaster. Two questionnaire surveys were conducted on people affected by the disaster to investigate the potential associations between diabetes and psychological distress, as well as breast cancer and reduced emotional happiness, with 680 and 582 participants, respectively. Additionally, we calculated the LHpLE owing to these risks. Although no significant reduction was found in emotional happiness due to diabetes or breast cancer, a significant reduction occurred due to psychological distress (0.265 and 0.476 for males and females, respectively). In the population aged 40–74 years, the LHpLE due to radiation-induced cancer, diabetes, and psychological distress were 0.0013, 0.14, and 0.21 years, respectively. This suggests that the association of LHpLE with diabetes and psychological distress was over two orders of magnitude greater than that associated with radiation-induced cancer. Within 7 years following the disaster, LHpLE due to diabetes increased, highlighting that diabetes is an ongoing issue. Therefore, this novel indicator of the LHpLE can provide a foundation for promoting effective public health measures following disasters.
SIV clearance from neonatal macaques following transient CCR5 depletion
Authors: Deere Jesse D. , Merriam David , Leggat Kawthar Machmach , Chang Wen-Lan William , Méndez-Lagares Gema , Kieu Hung , Dutra Joseph , Fontaine Justin , Lu Wenze , Chin Ning , Chen Connie , Tran Bryant Chi-Thien , Salinas Jessica , Miller Corey N. , Deeks Steven G. , Lifson Jeffrey D. , Engelman Kathleen , Magnani Diogo , Reimann Keith , Stevenson Mario , Hartigan-O’Connor Dennis J.
Published: May 2023

SUMMARY PARAGRAPH

Treatment of people with HIV (PWH) with antiretroviral therapy (ART) results in sustained suppression of viremia, but HIV persists indefinitely as integrated provirus in CD4-expressing cells. Intact persistent provirus, the “rebound competent viral reservoir” (RCVR), is the primary obstacle to achieving a cure. Most variants of HIV enter CD4+T cells by binding to the chemokine receptor, CCR5. The RCVR has been successfully depleted only in a handful of PWH following cytotoxic chemotherapy and bone marrow transplantation from donors with a mutation inCCR5. Here we show that long-term SIV remission and apparent cure can be achieved for infant macaques via targeted depletion of potential reservoir cells that express CCR5. Neonatal rhesus macaques were infected with virulent SIVmac251, then treated with ART beginning one week after infection, followed by treatment with either a CCR5/CD3-bispecific or a CD4-specific antibody, both of which depleted target cells and increased the rate of plasma viremia decrease. Upon subsequent cessation of ART, three of seven animals treated with CCR5/CD3-bispecific antibody rebounded quickly and two rebounded 3 or 6 months later. Remarkably, the other two animals remained aviremic and efforts to detect replication-competent virus were unsuccessful. Our results show that bispecific antibody treatment can achieve meaningful SIV reservoir depletion and suggest that functional HIV cure might be achievable for recently infected individuals having a restricted reservoir.
Complement C3 reduces apoptosis in human cardiomyocytes
Authors: Fang Zhou , Li Xiang , Yang Fajun , Xiaoli Alus Michael , Zhang Ming
Published: May 2023

Complement C3 is a key factor in complement system. Our recently animal study found that C3 may regulate myocardial apoptosis through the intrinsic apoptosis pathway. The current work investigated if C3 regulation of apoptosis occurred in human cardiomyocytes. Our results showed that incubation of exogenous C3 reduced apoptosis in a cell culture system of human cardiomyocytes which did not inherently express C3. In addition, C3 inhibited intrinsic apoptosis pathway in a cell-free apoptosis system. Furthermore, pro-C3 was found to bind with an apoptotic factor, pro-caspase 3, in a cell-free system. Thus, we presented firsthand evidence that exogenous C3 is readily reduce apoptosis in human cardiomyocytes via interaction with the intrinsic apoptotic pathway.
Distinct regions of the kinesin-5 C-terminal tail are essential for mitotic spindle midzone localization and sliding force
Authors: Gergely Zachary R. , Jones Michele H. , Zhou Bojun , Cash Cai , McIntosh J. Richard , Betterton Meredith D.
Published: May 2023

Kinesin-5 motor proteins play essential roles during mitosis in most organisms. Their tetrameric structure and plus-end-directed motility allow them to bind to and move along antiparallel microtubules, thereby pushing spindle poles apart to assemble a bipolar spindle. Recent work has shown that the C-terminal tail is particularly important to kinesin-5 function: the tail affects motor domain structure, ATP hydrolysis, motility, clustering, and sliding force measured for purified motors, as well as motility, clustering, and spindle assembly in cells. Because previous work has focused on presence or absence of the entire tail, the functionally important regions of the tail remain to be identified. We have therefore characterized a series of kinesin-5/Cut7 tail truncation alleles in fission yeast. Partial truncation causes mitotic defects and temperature-sensitive growth, while further truncation that removes the conserved BimC motif is lethal. We compared the sliding force generated bycut7mutants using a kinesin-14 mutant background in which some microtubules detach from the spindle poles and are pushed into the nuclear envelope. These Cut7-driven protrusions decreased as more of the tail was truncated, and the most severe truncations produced no observable protrusions. Our observations suggest that the C-terminal tail of Cut7p contributes to both sliding force and midzone localization. In the context of sequential tail truncation, the BimC motif and adjacent C-terminal amino acids are particularly important for sliding force. In addition, moderate tail truncation increases midzone localization, but further truncation of residues N-terminal to the BimC motif decreases midzone localization.
scDisInFact: disentangled learning for integration and prediction of multi-batch multi-condition single-cell RNA-sequencing data
Authors: Zhang Ziqi , Zhao Xinye , Qiu Peng , Zhang Xiuwei
Published: May 2023

Single-cell RNA-sequencing (scRNA-seq) has been widely used for disease studies, where sample batches are collected from donors under different conditions including demographical groups, disease stages, and drug treatments. It is worth noting that the differences among sample batches in such a study are a mixture of technical confounders caused by batch effect and the biological variations caused by condition effect. However, current batch effect removal methods often eliminate both technical batch effects and meaningful condition effects, while perturbation prediction methods solely focus on condition effects, resulting in inaccurate gene expression predictions due to unaccounted batch effects.

Here we introduce scDisInFact, a deep learning framework that models both batch effect and condition effect in scRNA-seq data. scDisInFact learns latent factors that disentangle condition effects from batch effects, enabling it to simultaneously perform three tasks: batch effect removal, condition-associated key gene detection, and perturbation prediction. We evaluated scDisInFact on both simulated and real datasets, and compared its performance to baseline methods for each task. Our results demonstrate that scDisInFact outperforms existing methods that focus on individual tasks, providing a more comprehensive and accurate approach for integrating and predicting multi-batch multi-condition single-cell RNA-sequencing data.