bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of Buyang Huanwu Decoction in patients with spinal cord injury: A meta-analysis of randomized controlled trials
Authors: He Zhongcheng , Yang Silin , Tan Yuxi , Liao Yulin , Song Shigang
Published: April 2024

Background:

There has been growing interest in using the traditional Chinese herb Buyang Huanwu Decoction (BHD) as a potential treatment for spinal cord injury (SCI), owing to its long-used treatment for SCI in China. However, the efficacy and safety of BHD treatment for SCI remain widely skeptical. This meta-analysis aims to assess the safety and efficacy of BHD in managing SCI.

Method:

A comprehensive literature search was conducted across several databases, including PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, VIP, and Sinomed, up to January 1, 2024. Randomized controlled clinical trials evaluating the safety or efficacy of BHD in SCI treatment were included. The analysis focused on 8 critical endpoints: Patient-perceived total clinical effective rate, American Spinal Cord Injury Association (ASIA) sensory score, ASIA motor score, somatosensory evoked potential, motor evoked potential, visual analog scale pain score, Japanese Orthopaedic Association score, and adverse events.

Results:

Thirteen studies comprising 815 participants met the inclusion criteria. No significant heterogeneity or publication bias was observed across the trials. The findings revealed significant improvements in the patient-perceived total clinical effective rate (OR = 3.77; 95% confidence interval [CI] = [2.43, 5.86]; P < .001), ASIA sensory score (mean difference [MD] = 8.22; 95% CI = [5.87, 10.56]; P < .001), ASIA motor score (MD = 7.16; 95% CI = [5.15, 9.18]; P < .001), somatosensory evoked potential (MD = 0.25; 95% CI = [0.03, 0.48]; P = .02), motor evoked potential (MD = 0.30; 95% CI = [0.14, 0.46]; P = .0002), and Japanese Orthopaedic Association score (MD = 1.99; 95% CI = [0.39, 3.58]; P = .01) in the BHD combination group compared to the control group. Additionally, there was a significant reduction in visual analog scale pain scores (MD = −0.81; 95% CI = [−1.52, −0.11]; P = .02) with BHD combination treatment, without a significant increase in adverse effects (OR = 0.68; 95% CI = [0.33, 1.41]; P = .3).

Conclusion:

The current evidence suggests that BHD is effective and safe in treating SCI, warranting consideration as a complementary and alternative therapy. However, given the low methodological quality of the included studies, further rigorous research is warranted to validate these findings.
Endovascular treatment of wide-neck bifurcation aneurysms using pCONUS2 HPC bridging device with single antiplatelet: A Case Series
Authors: Ho Jun Kiat , Kee Tze Phei , Lee Wickly
Published: April 2024

Rationale:

Wide neck bifurcation aneurysms (WNBA) are technically challenging for both surgical and endovascular treatments. Endovascular treatment for WNBA often requires dual antiplatelet therapy (DAPT) post stent insertion. Novel devices such as the pCONUS2 HPC neck bridging device have an HPC coating which reduces the device thrombogenicity. This theoretically allows for use of single antiplatelet therapy (SAPT), which would be advantageous, particularly in treating ruptured aneurysms. This case series aims to evaluate the safety of SAPT regimen only post stent insertion, by presenting our center early clinical experience in using pCONUS2 HPC neck bridging device in patients that are not suitable for DAPT.

Patient concerns:

We report the cases of 3 patients (2 females, 1 male; range: 64–71 years old) who underwent coil embolization for WNBA using the pCONUS2 HPC device (2 unruptured WNBA, and 1 ruptured WNBA). As all 3 patients were allergic to Aspirin, they could only be started on SAPT post endovascular therapy.

Diagnosis:

All 3 patients were diagnosed with WNBA on angiographic studies. Patient 1 had an unruptured left middle cerebral artery aneurysm; Patient 2 had a ruptured basilar tip aneurysm; Patient 3 had an unruptured anterior communicating artery (ACOM) aneurysm.

Interventions:

All 3 WNBA were treated with pCONUS2 HPC neck bridging device.

Outcomes:

There were no immediate complications. The immediate angiographic result of aneurysm treatment in Patient 1 and Patient 2 demonstrated incomplete occlusions, with delayed complete occlusion of aneurysm in Patient 1 and growth of aneurysmal neck in Patient 2 on follow-up angiograms (range: 6–9 months). No major thrombo-embolic or hemorrhagic complications in the first 2 patients. For Patient 3, the immediate angiographic result of the treated aneurysm demonstrated complete occlusion. However, the patient readmitted 11 days post procedure with cerebral infarction, scoring 5 on the modified Rankin scale on discharge.

Lessons:

pCONUS2 HPC as a neck bridging device in treating WNBA has yet to be shown superior to traditional techniques and devices. The theoretical advantage of HPC coating reducing its thrombogenicity requiring only SAPT is yet to be proven safe in clinical practice.
Breast mucosa-associated lymphoid tissue lymphoma: A case report and literature review
Authors: Luo Siyi , Zhang Xinyue , Wang Zhichun
Published: April 2024

Background:

Mucosa-associated lymphoid tissue (MALT) lymphoma, also known as extranodal marginal zone lymphoma, is more commonly detected in the stomach and rarely in the breast. Our study presented a clinical and pathological examination of a patient diagnosed with breast MALT lymphoma, supplemented with pertinent research, to offer guidance for the diagnosis and treatment of this condition.

People concerns:

The occurrence of breast MALT lymphoma has risen in the past decade, but its etiology, progression and treatment response are less well-studied.

Diagnosis:

Breast MALT lymphoma was diagnosed by excisional biopsy and histopathology.

Interventions:

Following breast MALT lymphoma diagnosis, the patient was transferred to the hematology department for further treatment, and she made the decision to continue observing.

Outcomes:

After 3 months of observation, the patient remained asymptomatic.

Conclusion:

Breast MALT lymphoma is an indolent disease with an asymptomatic presentation, There are no standardized treatment guidelines for breast MALT lymphoma, treatment must be tailored to the patient willingness to treat and the severity of the disease. Hence, in order to give patients a better chance of cure, more research is needed to explore its pathogenesis and more clinical trials are needed investigate the treatment of this disease.
Acute blockage of forearm supination due to flap tear of the triangular fibrocartilage disc: A case report
Authors: HO Ji Woong , Kim Jee Yune , Lee Young-Keun
Published: April 2024

Rationale:

Acute blockage of forearm supination has been reported in several studies. It is caused by loose bodies in the wrist joint, extensor carpi ulnaris tendon interposition, and distal radioulnar joint (DRUJ) injuries, including forearm bone fractures. Some studies have reported cases of DRUJ injuries caused by triangular fibrocartilage complex (TFCC) tears.

We report a case of acute blockage of forearm supination after minor trauma and suggest a possible TFCC tear when a patient complains of forearm supination blocking. In addition, we present a comparison between our case and other reports on etiology, magnetic resonance imaging (MRI) findings, and arthroscopic findings, and show the specific characteristics of our case.

Patients concerns:

A 22-year-old male presented with left wrist pain as the chief complaint. He was injured 2 months prior to pushing his left hand on the floor during exercise. Physical examination showed a relative limitation of range of motion (ROM) in the left wrist of about 10° in flexion and about 15° in extension compared with the right side. The patient also complained of supination limitation and volar side wrist pain during supination. The patient showed tenderness in the axial compression test.

Diagnoses:

Plain radiographs showing no abnormalities. MRI showed a TFCC tear in the central portion. A torn flap of the TFCC was interposed on the volar side of the DRUJ.

Interventions:

Arthroscopic surgery of the left wrist joint was performed. Arthroscopic examination revealed a tear in the TFCC on the radial side. A torn flap was interposed on the volar side of the DRUJ. We removed the flap from the DRUJ using an arthroscopic grasper and partially resected it.

Outcomes:

Intraoperative tests showed no locking and the forearm was well supinated. Two months after the surgery, the patient had no pain and showed full forearm supination.

Lessons:

DRUJ blocking due to a TFCC tear should be suspected when acute blockage of forearm supination occurs after minor trauma. MRI is helpful for diagnosis; however, we suggest that the diagnosis should be confirmed through arthroscopy. Symptoms can be resolved by surgical treatment using arthroscopy.
Epigenetics of hematopoietic stem cell aging
Authors: Yokomizo Takako , Oshima Motohiko , Iwama Atsushi
Published: April 2024

Purpose of review

The development of new antiaging medicines is of great interest to the current elderly and aging population. Aging of the hematopoietic system is attributed to the aging of hematopoietic stem cells (HSCs), and epigenetic alterations are the key effectors driving HSC aging. Understanding the epigenetics of HSC aging holds promise of providing new insights for combating HSC aging and age-related hematological malignancies.

Recent findings

Aging is characterized by the progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. During aging, the HSCs undergo both quantitative and qualitative changes. These functional changes in HSCs cause dysregulated hematopoiesis, resulting in anemia, immune dysfunction, and an increased risk of hematological malignancies. Various cell-intrinsic and cell-extrinsic effectors influencing HSC aging have also been identified. Epigenetic alterations are one such mechanism.

Cumulative epigenetic alterations in aged HSCs affect their fate, leading to aberrant self-renewal, differentiation, and function of aged HSCs. In turn, these factors provide an opportunity for aged HSCs to expand by modulating their self-renewal and differentiation balance, thereby contributing to the development of hematological malignancies.
Occipito-Cervico-Dorsal Flap for Neck Reconstruction After Postburn Contractures: A Case Report and Literature Review
Authors: Alvedro-Ruiz Pedro , Díaz-Ros Nerea , García-García María , Merino-Romero Mar , Heredia-Alcalde Iván , Andresen-Lorca Belén , Pérez-Plaza Aranzazu , Pérez-Del-Caz María Dolores
Published: April 2024

Because the head and neck are one of the most frequent locations of burns, it is of paramount importance that plastic surgeons and plastic surgical nurses understand the most effective surgical methods for treating neck contractures and the reconstructive technique required for each case. We introduce the case of a 42-year-old woman who presented with a severe postburn neck contracture that was reconstructed with a pedicled occipito-cervico-dorsal flap. We closed the donor-site wound primarily and completely covered the defect with good results. In addition to conventional skin grafts, dermal matrices, and microsurgical techniques, using an occipito-cervico-dorsal flap should be considered for reconstructing postburn neck contractures as it offers good aesthetic and functional outcomes, provides enough tissue and pliable skin, and results in minimal donor-site morbidity.
Cross Lip Vermilion Flap and Traumatic Upper Lip Avulsion: Reducing Donor Site Morbidity
Authors: Rahpeyma Amin , Khajehahmadi Saeedeh
Published: April 2024

Using a cross lip vermilion flap for upper red lip reconstruction in cases other than whistle deformity in patients with cleft lip can lead to donor site morbidity. If the practitioner performs primary closure of the mucosa in lower vermilion after flap harvesting, the width and height of lower lip are reduced, which results in an increased lower incisor tooth show. Using free fat grafting is an effective method for reducing donor site morbidity in the lower lip following cross lip vermilion flap harvest.
Tips for the Perfect Lips
Authors: Soroush Yalda
Published: April 2024

Lip augmentation can correct lip asymmetries, reduce fine lines, define lip shape and Cupid's bow, and add natural fullness to the lips. Achieving a perfect result when injecting lip filler is an art that combines the desire of the patient with the skill of the practitioner and the practitioner's understanding of the surrounding anatomy. It is essential for aesthetic practitioners to prioritize open communication, provide custom-tailored treatments, and have a strong commitment to achieving natural and harmonious results. By following these principles, patients can enjoy the benefits of enhanced lips that boost their self-confidence while maintaining their unique beauty.
Diagnostic Performance of 18F-FDG Positron Emission Tomography/Computed Tomography and Blood Test Parameters for Pulmonary Inflammatory Pseudotumor
Authors: Pan Bo , Wang Yanming , Zhu Zehua , Zhu Xingxing
Published: April 2024

Purpose:

Pulmonary inflammatory pseudotumor (PIP) is an inflammatory proliferative tumor-like lesion that frequently exhibits hypermetabolism on 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography imaging (PET/CT) and is readily misdiagnosed as a malignant tumor. The purpose of this study was to identify PIP by combining PET/computed tomography metabolic and blood test characteristics with machine learning.

Patients and Methods:

We recruited 27 patients with PIP and 28 patients with lung cancer (LC). The PET metabolic and blood test parameters were collected, and the differences between the groups were evaluated. In addition, we combined the support vector machine (SVM) classifier with the indicators that differed between the groups to classify PIP and LC.

Results:

For PET metabolic parameters, our findings showed that, as compared with the LC group, maximal standardized uptake value (P < 0.001, t = −4.780), Mean standardized uptake value SUVmean, P < 0.001, t = −4.946), and SD40% (P < 0.001, t = −4.893) were considerably reduced in the PIP group, whereas CV40% (P = 0.004, t = 3.012) was significantly greater. For blood test parameters, the total white blood cell count (P < 0.001, t = 6.457) and absolute neutrophil count (P < 0.001, t = 6.992) were substantially higher in the PIP group than in the LC group. Furthermore, the performance of SVM trained solely on PET metabolic parameters (mean area under the curve [AUC] = 0.84) was comparable to that of SVM trained solely on blood test parameters (mean AUC = 0.86). Surprisingly, utilizing the combined parameters increased SVM performance significantly (mean AUC = 0.98).

Conclusion:

PET metabolic and blood test parameters differed significantly between the PIP and LC groups, and the SVM paradigm using these significantly different features has the potential to be used to classify PIP and LC, which has important clinical implications.
Pudendal Block at the Time of Transvaginal Prolapse Repair: A Randomized Controlled Trial
Authors: Torosis Michele , Fullerton Morgan , Kaefer Daniela , Nitti Victor , Ackerman A. Lenore , Grisales Tamara
Published: April 2024

Importance

The utility of pudendal nerve blocks (PNBs) at the time of transvaginal surgery is mixed in the literature. No published study has evaluated the efficacy of PNB since the widespread adoption of Enhanced Recovery After Surgery (ERAS) pathways.

Objective

This study aimed to determine if PNB, in addition to ERAS measures, at the time of vaginal reconstructive surgery reduces opioid use in the immediate postoperative period.

Study Design

In this randomized, blinded, controlled trial, women scheduled for transvaginal multicompartment prolapse repair were randomized to bilateral PNB before incision with 20 mL of 0.5% bupivacaine versus usual care. Primary outcome was opioid use in morphine milligram equivalents (MME) for the first 24 hours. The study was powered to detect a 5.57-MME difference in opioid use in the first 24 hours between groups.

Results

Forty-four patients were randomized from January 2020 to April 2022. The PNB and control groups were well matched in demographic and surgical data. There was no difference in opioid use in first 24 hours between the control and PNB groups (8 [0–20] vs 6.7 [0–15]; P = 0.8). Median pain scores at 24 and 48 hours did not differ between groups (4 ± 2 vs 3 ± 3; P = 0.44) and 90% of participants were satisfied with pain control across both groups. Time to return to normal activities (median, 10 days) was also not different between the groups.

Conclusions

Because pain satisfaction after transvaginal surgery in the era of ERAS is high, with overall low opioid requirements, PNB provides no additional benefit.
Genome sequence of the bialaphos producer Streptomyces sp. DSM 41527 and two putative phosphonate antibiotic producers Streptomyces sp. DSM 41014 and DSM 41981 from the DSMZ strain collection
Authors: Zimmermann Alina , Nouioui Imen , Mast Yvonne
Published: April 2024

Streptomyces sp. DSM 41014, DSM 41527, and DSM 41981 are three strains from the DSMZ strain collection. Here, we present the draft genome sequences of DSM 41014, DSM 41527, and DSM 41981 with a size of 9.09 Mb, 8.45 Mb, and 9.23 Mb, respectively.
Overcome the Limitation of Phenome-Wide Association Studies (PheWAS): Extension of PheWAS to Efficient and Robust Large-Scale ICD Codes Analysis
Authors: Lin Ya−Chen , Zhang Siwei , Vessels Tess , Bastarache Lisa , Bejan Cosmin Adrian , Hsie Ryan S , Philips Elizabeth J , Ruderfer Doug M , Pulley Jill M. , Edwards Todd L , Wells Quinn S , Warner Jeremy L , Denny Joshua C , Roden Dan M , Kang Hakmook , Xu Yaomin
Published: April 2024

The Phenome-wide association studies (PheWAS) have become widely used for efficient, high-throughput evaluation of relationship between a genetic factor and a large number of disease phenotypes, typically extracted from a DNA biobank linked with electronic medical records (EMR). Phecodes, billing code-derived disease case-control status, are usually used as outcome variables in PheWAS and logistic regression has been the standard choice of analysis method. Since the clinical diagnoses in EMR are often inaccurate with errors which can lead to biases in the odds ratio estimates, much effort has been put to accurately define the cases and controls to ensure an accurate analysis. Specifically in order to correctly classify controls in the population, an exclusion criteria list for each Phecode was manually compiled to obtain unbiased odds ratios. However, the accuracy of the list cannot be guaranteed without extensive data curation process. The costly curation process limits the efficiency of large-scale analyses that take full advantage of all structured phenotypic information available in EMR. Here, we proposed to estimate relative risks (RR) instead. We first demonstrated the desired nature of RR that overcomes the inaccuracy in the controls via theoretical formula. With simulation and real data application, we further confirmed that RR is unbiased without compiling exclusion criteria lists. With RR as estimates, we are able to efficiently extend PheWAS to a larger-scale, phenome construction agnostic analysis of phenotypes, using ICD 9/10 codes, which preserve much more disease-related clinical information than Phecodes.
Enhancing Prosthetic Vision by Upgrade of a Subretinal Photovoltaic Implant in situ
Authors: Bhuckory Mohajeet B. , Monkongpitukkul Nicharee , Shin Andrew , Goldstein Anna Kochnev , Jensen Nathan , Shah Sarthak V , Pham-Howard Davis , Butt Emma , Dalal Roopa , Galambos Ludwig , Mathieson Keith , Kamins Theodore , Palanker Daniel
Published: April 2024

In patients with atrophic age-related macular degeneration, subretinal photovoltaic implant (PRIMA) provided visual acuity up to 20/440, matching its 100μm pixels size. Next-generation implants with smaller pixels should significantly improve the acuity. This study in rats evaluates removal of a subretinal implant, replacement with a newer device, and the resulting grating acuity in-vivo. Six weeks after the initial implantation with planar and 3-dimensional devices, the retina was re-detached, and the devices were successfully removed. Histology demonstrated a preserved inner nuclear layer. Re-implantation of new devices into the same location demonstrated retinal re-attachment to a new implant. New devices with 22μm pixels increased the grating acuity from the 100μm capability of PRIMA implants to 28μm, reaching the limit of natural resolution in rats. Reimplanted devices exhibited the same stimulation threshold as for the first implantation of the same implants in a control group. This study demonstrates the feasibility of safely upgrading the subretinal photovoltaic implants to improve prosthetic visual acuity.
Molecular fingerprints of cell size sensing and mating type differentiation in pennate diatoms
Authors: Belišová Darja , Bilcke Gust , Audoor Sien , D’hondt Sofie , De Veylder Lieven , Vandepoele Klaas , Vyverman Wim
Published: April 2024

A unique cell size sensing mechanism is at the heart of the life cycle of diatoms. During population growth, cell size decreases until a Sexual Size Threshold (SST) is reached, below which cells become sexually competent. In most pennate diatoms, the two mating types undergo biochemical and behavioral differentiation below the SST, although the molecular pathways underlying their size-dependent maturation remain unknown.

Here, we developed a method to shorten the generation time ofCylindrotheca closteriumthrough single-cell microsurgery, enabling the transcriptomic comparison of genetically identical large and undifferentiated cells with small, sexually competent cells for six different genotypes.

We identified 21 genes upregulated in small cells regardless of their mating type, revealing how cells undergo specific transcriptional reprogramming when passing the SST. Furthermore, we revealed a size-regulated gene cluster with three mating type-specific genes susceptible to sex-inducing pheromones. In addition, comparative transcriptomics confirmed the shared mating type specificity of Mating-type Related Minus 2 homologs in three pennate diatoms, suggesting them to be part of a conserved partner-recognition mechanism.

This study sheds light on how diatoms acquire sexual competence in a strictly size-dependent manner, revealing a complex machinery underlying size-dependent maturation, mating behavior, and heterothally in pennate diatoms.
Opaque Ontology: Neuroimaging Classification of ICD-10 Diagnostic Groups in the UK Biobank
Authors: Easley Ty , Luo Xiaoke , Hannon Kayla , Lenzini Petra , Bijsterbosch Janine D
Published: April 2024

Background: The use of machine learning to classify diagnostic cases versus controls defined based on diagnostic ontologies such as the ICD-10 from neuroimaging features is now commonplace across a wide range of diagnostic fields. However, transdiagnostic comparisons of such classifications are lacking. Such transdiagnostic comparisons are important to establish the specificity of classification models, set benchmarks, and assess the value of diagnostic ontologies. Results: We investigated case-control classification accuracy in 17 different ICD-10 diagnostic groups from Chapter V (mental and behavioral disorders) and Chapter VI (diseases of the nervous system) using data from the UK Biobank. Classification models were trained using either neuroimaging (structural or functional brain MRI feature sets) or socio-demographic features. Random forest classification models were adopted using rigorous shuffle splits to estimate stability as well as accuracy of case-control classifications. Diagnostic classification accuracies were benchmarked against age classification (oldest versus youngest) from the same feature sets and against additional classifier types (K-nearest neighbors and linear support vector machine). In contrast to age classification accuracy, which was high for all feature sets, few ICD-10 diagnostic groups were classified significantly above chance (namely, demyelinating diseases based on structural neuroimaging features, and depression based on socio-demographic and functional neuroimaging features). Conclusion: These findings highlight challenges with the current disease classification system, leading us to recommend caution with the use of ICD-10 diagnostic groups as target labels in brain-based disease prediction studies.
Homeostats – the hidden rulers of ion homeostasis in plants
Authors: Dreyer Ingo , Hernández-Rojas Naomí , Bolua-Hernández Yasnaya , de los Angeles Tapia-Castillo Valentina , Astola-Mariscal Sadith Zobeida , Díaz-Pico Erbio , Mérida-Quesada Franko , Vergara-Valladares Fernando , Arrey-Salas Oscar , Rubio-Meléndez María Eugenia , Riedelsberger Janin , Michard Erwan
Published: April 2024

Ion homeostasis is a crucial process in plants that is closely linked to the efficiency of nutrient uptake, stress tolerance and overall plant growth and development. Nevertheless, our understanding of the fundamental processes of ion homeostasis is still incomplete and highly fragmented. Especially at the mechanistic level, we are still in the process of dissecting physiological systems to analyze the different parts in isolation. However, modeling approaches have shown that it is not individual transporters but rather transporter networks (homeostats) that control membrane transport and associated homeostatic processes in plant cells. To facilitate access to such theoretical approaches, the modeling of the potassium homeostat is explained here in detail to serve as a blueprint for other homeostats. Based on a few, elementary knowledge about the thermodynamics of the different transport processes, it is possible to draw fundamental conclusions about the properties and physiology of the transporter network.
Systems Neuroscience Computing in Python (SyNCoPy): A Python Package for Large-scale Analysis of Electrophysiological Data
Authors: Mönke Gregor , Schäfer Tim , Parto-Dezfouli Mohsen , Kajal Diljit Singh , Fürtinger Stefan , Schmiedt Joscha Tapani , Fries Pascal
Published: April 2024

We introduce an open-source Python package for the analysis of large-scale electrophysiological data called SyNCoPy, for Systems Neuroscience Computing in Python. The package includes signal processing analyses across time (e.g. time-lock analysis), frequency (e.g. power spectrum), and connectivity (e.g. coherence) domains. It enables user-friendly data analysis on both laptop-based and high-performance computing systems. SyNCoPy is designed to facilitate trial-parallel workflows (parallel processing of trials) making it an ideal tool for large-scale analysis of electrophysiological data. Based on parallel processing of trials, the software can support very large-scale datasets via innovative out-of-core computation techniques. It also provides seamless interoperability with other standard software packages through a range of file format importers and exporters and open file formats. The naming of the user functions closely follows the well-established FieldTrip framework, which is an open-source Matlab toolbox for advanced analysis of electrophysiological data.
EcoHIV Infection Modulates the Effects of Cocaine Exposure Pattern and Abstinence on Cocaine Seeking and Neuroimmune Protein Expression in Male Mice
Authors: Namba Mark D. , Xie Qiaowei , Park Kyewon , Jackson Joshua G. , Barker Jacqueline M.
Published: April 2024

Cocaine use disorders (CUDs) and human immunodeficiency virus (HIV) remain persistent public health dilemmas throughout the world. One major hurdle for treating CUD is the increase in cocaine craving and seeking behavior that occurs over a protracted period of abstinence, an effect known as the incubation of craving. Little is known about how HIV may modulate this process. Thus, we sought to examine the impact of chronic HIV infection on the incubation of cocaine craving and associated changes in the central and peripheral immune systems. Here, mice were inoculated with EcoHIV, which is a chimeric HIV-1 construct that produces chronic HIV infection in mice. EcoHIV- and sham- infected mice were conditioned with cocaine daily or intermittently in a conditioned place preference (CPP) paradigm, followed by 1 or 21 days of forced abstinence prior to assessing preference for the cocaine-paired chamber. Under both conditioning regimens, sham mice exhibited incubation of cocaine CPP after 21 days of abstinence. EcoHIV- infected mice conditioned daily with cocaine showed enhanced cocaine seeking at both abstinence timepoints, whereas infected mice conditioned intermittently showed a reversal of the incubation effect, with higher cocaine seeking after 1 day of abstinence compared to 21 days. Analysis of corticolimbic CX3CL1-CX3CR1 and glutamate receptor expression revealed alterations in medial prefrontal cortex (mPFC) CX3CL1 and nucleus accumbens (NAc) GluN2A receptors that correlated with cocaine seeking following daily cocaine exposure. Moreover, examination of peripheral immune markers showed that the effect of abstinence and EcoHIV infection on these measures depended on the cocaine exposure regimen. Altogether, these results highlight the importance of cocaine abstinence and exposure pattern as critical variables that modulate HIV-associated neuroimmune outcomes and relapse vulnerability.
A Status-Neutral Approach to HIV – Is Targeted Testing Still Relevant South of Sahara?
Authors: Mugauri Hamufare , Mugurungi Owen , Chirenda Joconiah , Takarinda Kudakwashe , Mangwiro Prosper , Tshimanga Mufuta
Published: April 2024

Introduction

In 2022, UNAIDS replaced the 90% Global HIV targets with six Comprehensive 95% targets that include linkage to comprehensive HIV prevention services, the thrust of the status-neutral approach to HIV testing. Zimbabwe has been implementing both targeted testing and the status-neutral concept. In this paper, we analyse the role of status-neutral concepts in targeted testing, for effective case identification and linkage to prevention and treatment services.

Methods

We conducted a cross-sectional study on 36 multi-stage sampled sites across 4/10 provinces of Zimbabwe. Screened and non-screened patients were tested and analysed for positivity ratios and linkage to post-test services. Data were extracted using Epicollect5 and imported into EpiData software and Stata for cleaning and analysis. Data were summarized as proportions, odds ratios and adjusted odds ratios at 5% significance level.

Results

Of 23,058 HIV tests done, females constituted 55% (n=12,698), whilst 63.5% (n=14,650) were retests and positivity of 7.5% obtained. Screened patients contributed 75.1% to the overall positivity (1,296/1,727), from 66% (n=15,289) of the total tests conducted. The 45–49-year category was 3.6 times more likely to test positive (a95%CI:2.67,4.90). Males were 3.09 times more likely to test positive in adjusted analysis (a95%CI: 2.74, 3.49), from an 8% (n=912) positivity ratio. First tests were 65% more likely to test HIV positive (a95%CI: 1.43, 1.91) whilst screened patients were 3.89 times more likely to link to HIV prevention services (a95%CI: 3.05, 4.97), against 25.5% (n=1,871) linkage among patients not screened

Conclusion

Targeted and status-neutral testing are related and complimentary concepts which, when simultaneously applied, potentiates case identification through prioritizing high-risk individuals for testing, as well as arresting ongoing transmission of HIV through effective linkage to HIV prevention and treatment. This approach facilitates economic usage of limited resources, in generalized epidemics.
What role do community-level factors play in HIV self-testing uptake, linkage to services and HIV-related outcomes? A mixed methods study of community-led HIV self-testing programmes in rural Zimbabwe
Authors: Tumushime Mary K , Ruhode Nancy , Neuman Melissa , Watadzaushe Constancia , Mutseta Miriam , Taegtmeyer Miriam , Johnson Cheryl C. , Hatzold Karin , Corbett Elizabeth L. , Cowan Frances M. , Sibanda Euphemia L.
Published: April 2024

Community-led interventions, where communities plan and lead implementation, are increasingly adopted in public health. We explore what factors may be associated with successful community-led distribution of HIV self-test (HIVST) kits to guide future service delivery.

Twenty rural communities were supported to implement month-long HIVST kit distribution programmes from January-September/2019. Participant observation was conducted to document distribution models. Three months post-intervention, a population-based survey measured: self-reported new HIV diagnosis; self-reported HIVST uptake; self-reported linkage to post-test services; and viral load. The survey included questions for a composite measure of ‗community cohesion‘. Communities were grouped into low/medium/high based on community cohesion scores. We used mixed effect logistic regression to assess how outcomes differed by community cohesion. In total, 27,812 kits were distributed by 348 distributors. Two kit distribution models were implemented: door-to-door distribution only or distribution at venues/events within communities. Of 5,683 participants surveyed, 1,831 (32.2%) received kits and 1,229 (67.1%) reported using it; overall HIVST uptake was 1,229/5,683 (21.6%). Self-reported new HIV diagnosis increased with community cohesion, from 32/1,770 (1.8%) in the lowest cohesion group to 40/1,871 (2.1%) in the medium group, adjusted odds ratio (aOR) 2.94 (1.41-6.12, p=0.004) and 66/2,042 (3.2%) in the highest cohesion group, aOR 7.20 (2.31-22.50, p=0.001). Other outcomes did not differ by extent of cohesion.

HIVST kit distribution in high-cohesion communities was associated with seven times higher odds of identifying people with new HIV diagnoses, suggesting more cohesive communities may better identify those most at risk of undiagnosed HIV. Communities can learn from and adopt these participatory community-led approaches to intervention planning and implementation, which may foster cohesion and benefit public health programmes.
Improving 10-year cardiovascular risk prediction in patients with type 2 diabetes with metabolomics
Authors: Xie Ruijie , Seum Teresa , Sha Sha , Trares Kira , Holleczek Bernd , Brenner Hermann , Schöttker Ben
Published: April 2024

Background and Aims

To evaluate the potential of improved prediction of the 10-year risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes by adding metabolomic biomarkers to the SCORE2-Diabetes model.

Methods

Data from 10,257 and 1,039 patients with type 2 diabetes from the UK Biobank (UKB) and the German ESTHER cohort, respectively, were used for model derivation, internal and external validation. A total of 249 metabolites were measured with nuclear magnetic resonance (NMR) spectroscopy. LASSO regression with bootstrapping was used to identify metabolites in sex-specific analyses and the predictive performance of metabolites added to the SCORE2-Diabetes model was primarily evaluated with Harrell’s C-index.

Results

Seven metabolomic biomarkers were selected by LASSO regression for enhanced MACE risk prediction (three for both sexes, three male- and one female-specific metabolite(s)). Especially albumin and the omega-3-fatty-acids-to-total-fatty-acids-percentage among males and lactate among females improved the C-index. In internal validation with 30% of the UKB, adding the selected metabolites to the SCORE2-Diabetes model increased the C-index statistically significantly (P=0.034) from 0.660 to 0.680 in the total sample. In external validation with ESTHER, the C-index increase was higher (+0.041) and remained statistically significant (P=0.015).

Conclusions

Incorporating seven metabolomic biomarkers in the SCORE2-Diabetes model enhanced its ability to predict MACE in patients with type 2 diabetes. Given the latest cost reduction and standardization efforts, NMR metabolomics has the potential for translation into the clinical routine.
Fiberscopic Pattern Removal for Optimal Coverage in 3D Bladder Reconstructions of Fiberscope Cystoscopy Videos
Authors: Eimen Rachel , Krzyzanowska Halina , Scarpato Kristen R. , Bowden Audrey K.
Published: April 2024

Purpose

In the current clinical standard of care, cystoscopic video is not routinely saved because it is cumbersome to review. Instead, clinicians rely on brief procedure notes and still frames to manage bladder pathology. Preserving discarded data via 3D reconstructions, which are convenient to review, has the potential to improve patient care. However, many clinical videos are collected by fiberscopes, which are lower cost but induce a pattern on frames that inhibits 3D reconstruction. The aim of this study is to remove the honeycomb-like pattern present in fiberscope-based cystoscopy videos to improve the quality of 3D bladder reconstructions.

Approach

This study introduces a novel algorithm that applies a notch filtering mask in the Fourier domain to remove the honeycomb-like pattern from clinical cystoscopy videos collected by fiberscope as a preprocessing step to 3D reconstruction. We produce 3D reconstructions with the video before and after removing the pattern, which we compare with a novel metric termed the area of reconstruction coverage (ARC), defined as the surface area (in pixels) of the reconstructed bladder. All statistical analyses use paired t-tests.

Results

Preprocessing using our method for pattern removal enabled reconstruction for all (n = 5) cystoscopy videos included in the study and produced a statistically significant increase in bladder coverage (p = 0.018).

Conclusions

This algorithm for pattern removal increases bladder coverage in 3D reconstructions and automates mask generation and application, which could aid implementation in time-starved clinical environments. The creation and use of 3D reconstructions can improve documentation of cystoscopic findings for future surgical navigation, thus improving patient treatment and outcomes.
Associations Between Exercise Capacity and Psychological Functioning in Children and Adolescents with Fontan Circulation
Authors: Seivert Nicholas P. , Dodds Kathryn M. , O’Malley Shannon , Goldberg David J. , Paridon Stephen , McBride Michael , Rychik Jack
Published: April 2024

Background

Pediatric patients with Fontan circulation (FC) often have diminished exercise capacity. They are also at risk for psychological problems, including anxiety, depression, and inattention. The current study examines associations between exercise capacity and psychological functioning in a clinical sample of pediatric patients with FC.

Methods

A multidisciplinary team evaluated participants in a dedicated clinic for pediatric patients with FC. Patients completed cardiopulmonary exercise testing (CPET); metrics selected for analyses included peak oxygen consumption (VO2), maximum achieved heart rate (HR), oxygen saturation at peak exercise, ventilatory anaerobic threshold, work rate, respiratory exchange ratio, and HR recovery at 1-, 3-, and 8-minutes after exercise. Parent and child were administered a standardized questionnaire to measure depression, anxiety, and inattention symptoms. Patients who completed CPET with adequate effort and a psychological measure were eligible for inclusion. Clinical data were extracted from medical records and analyzed using Pearson correlations.

Results

Clinical sample (n = 51) was 55% male with a mean age of 13.6 years (SD=2.5). A majority had hypoplastic left heart syndrome (51%). There was a significant negative correlation between parent-report of inattention and peak VO2 (R= -.307, 95% CI -.549/-.018,P= 0.038). Self-report of anxiety was positively correlated with HR recovery at 3 (R= .438, 95% CI .155/.655,P= 0.004) and 8 (R= .432, 95% CI .147/.651,P= 0.004) minutes post exercise. Depression was positively correlated with HR recovery at 3 minutes for parent report (R= .294, 95% CI .004/.538,P= 0.047) and 8 minutes for self-report (R= .410, 95% CI .122/.635,P= 0.007).

Conclusions

Inattention, depression, and anxiety symptoms were correlated with some CPET metrics in our clinical sample of pediatric patients with FC. Greater inattention symptoms were associated with lower peak VO2. Those with greater depression and anxiety symptoms showed a more rapid decline from max HR to recovery period.

What is Known

Many patients with Fontan circulation (FC) have some degree of diminished exercise capacity.

The risk for mental health problems in pediatric patients with FC is very high, with an estimated lifetime prevalence of 65%.

What the Study Adds

There may be a link between mental health symptoms and exercise capacity metrics obtained during CPET for children and adolescents with FC.

Our study found that greater inattention symptoms were linked to lower observed peak VO2 during CPET.

Participants with higher levels of depression and anxiety symptoms exhibited a more dramatic decline in HR after exercise, contrary to findings in other cardiac patient samples that report an attenuated HR response for those with depression and anxiety.
A generalized framework to identify SARS-CoV-2 broadly neutralizing antibodies
Authors: Jian Fanchong , Wec Anna Z. , Feng Leilei , Yu Yuanling , Wang Lei , Wang Peng , Yu Lingling , Wang Jing , Hou Jacob , Berrueta Daniela Montes , Lee Diana , Speidel Tessa , Ma LingZhi , Kim Thu , Yisimayi Ayijiang , Song Weiliang , Wang Jing , Liu Lu , Yang Sijie , Niu Xiao , Xiao Tianhe , An Ran , Wang Yao , Shao Fei , Wang Youchun , Henry Carole , Pecetta Simone , Wang Xiangxi , Walker Laura M. , Cao Yunlong
Published: April 2024

Monoclonal antibodies (mAbs) targeting the SARS-CoV-2 receptor-binding domain (RBD) showed high efficacy in the prevention and treatment of COVID-19. However, the rapid evolution of SARS-CoV-2 has rendered all clinically authorized mAbs ineffective and continues to stymie the development of next-generation mAbs. Consequently, the ability to identify broadly neutralizing antibodies (bnAbs) that neutralize both current and future variants is critical for successful antibody therapeutic development, especially for newly emerged viruses when no knowledge about immune evasive variants is available. Here, we have developed a strategy to specifically select for potent bnAbs with activity against both existing and prospective SARS-CoV-2 variants based on accurate viral evolution prediction informed by deep mutational scanning (DMS). By adopting this methodology, we increased the probability of identifying XBB.1.5-effective SARS-CoV-2 bnAbs from ∼1% to 40% if we were at the early stage of the pandemic, as revealed by a retrospective analysis of >1,000 SARS-CoV-2 wildtype (WT)-elicited mAbs. From this collection, we identified a bnAb, designated BD55-1205, that exhibited exceptional activity against historical, contemporary, and predicted future variants. Structural analyses revealed extensive polar interactions between BD55-1205 and XBB.1.5 receptor-binding motif (RBM), especially with backbone atoms, explaining its unusually broad reactivity. Importantly, mRNA-based delivery of BD55-1205 IgG to human FcRn-expressing transgenic mice resulted in high serum neutralizing titers against selected XBB and BA.2.86 subvariants. Together, the ability to identify bnAbs via accurate viral evolution prediction, coupled with the speed and flexibility of mRNA delivery technology, provides a generalized framework for the rapid development of next-generation antibody-based countermeasures against SARS-CoV-2 and potentially other highly variable pathogens with pandemic potential.
Assessing visual performance during intense luminance changes in virtual reality
Authors: Domdei Niklas , Sauer Yannick , Hecox Brian , Neugebauer Alexander , Wahl Siegfried
Published: April 2024

During indoor-outdoor transitions humans encounter luminance changes beyond the functional range of the photoreceptors, leaving the individual at risk of overlooking harmful low-contrast objects until adaptation processes re-enable optimal vision. To study human visual performance during intense luminance changes, we propose a virtual reality based testbed. After linearization of the headset’s luminance output, detection times were recorded for ten participants. The small (FWHM = 0.6 degree) low-contrast stimuli appeared randomly in one of four corners (±10 degree) after luminance changes of three magnitudes within 1 or 3 seconds. Significantly decreased detection times were observed for the conditions with simulated self-tinting lenses compared to lenses with fixed transmission rates after luminance decreases. In cases of luminance increases all detection times were similar. In conclusion, the proposed virtual reality testbed allows for studying vision during or after steep luminance changes and helps to design technical aids like self-tinting lenses.

Highlights

The HTC Vive headset provides a practicable luminance range of 3 magnitudes, allowing the simulation of indoor-outdoor transitions.

Visual performance after steep luminance decreases was significantly better with simulated self-tinting spectacles reducing the encountered luminance step.

Different transmission rates of the simulated lenses did not affect the detection times for small low-contrast stimuli after luminance increases.
Moving towards precision TMS? Evaluating individual differences and reproducibility of personalized stimulation targets in UK Biobank
Authors: Zhao Ying , Zhao Yi-Jie , Cui Hailun , Bethlehem Richard A.I. , Voon Valerie
Published: April 2024

Objective

Personalized transcranial magnetic stimulation (TMS) targeting, guided by functional connectivity (FC), shows potential in treating depression. The present study aims to map individual FC peak location using UK Biobank, to evaluate individual differences and reproducibility of FC-based targets.

Methods

We analyzed UK Biobank resting-state fMRI (rfMRI) of 35,423 participants, identifying individual FC peak locations on the dorsolateral prefrontal cortex (DLPFC) that functionally connected to the subcallosal cingulate, amygdala, and ventromedial prefrontal cortex, respectively. Euclidean distance between each participant’s individual peak and group-average peak was calculated. With follow-up rfMRI of 1341 participants, within-subject FC peak location changes were calculated. We also compared common TMS targets and random locations for their median distance to individual peaks in a permutation test.

Results

Seed-based FC analyses revealed large differences in the individual FC peak location on DLPFC: the mean distance from the individual peaks to group-average peak ranged from 14.24 to 29.92mm; 70% to 94% of participants were >10mm away from the group-average peak and potentially located outside of the TMS effective area with common TMS coils. Similar variability was observed in within-subject peak locations across two fMRI assessments. Common TMS targets and the group-average FC peak showed no significant difference in median distances to individual FC peaks when compared to random locations.

Conclusions

FC peak location shows wide inter- and intra-individual variability. We emphasize a role for individualized TMS neuronavigation targeting but emphasize the need for more reliable biomarker studies.