bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical application of ultrasound-guided totally implantable venous access ports implantation via the posterior approach of the internal jugular vein
Authors: Wang Minghai , Tang Linna , Xu Rongwei , Qin Shiyong , Zhang Shuguang
Published: November 2023

Background:

To determine the feasibility and safety of ultrasound-guided totally implantable venous access port (TIVAP) implantation via the posterior approach of the internal jugular vein (IJV).

Methods:

From September 2021 to August 2022, 88 oncology patients underwent ultrasound-guided implantation of TIVAPs via the posterior approach of the IJV for the administration of chemotherapy. The catheter tip was adjusted to be positioned at the cavoatrial junction under fluoroscopic guidance. Clinical data including surgical success, success rate for the first attempt, intraoperative, and postoperative complications were all collected and analyzed.

Results:

All patients underwent successful surgery (100%), whereby 58 were via the right IJV and 30 via the left IJV, and the success rate for the first attempt was 96.59% (85/88). The operation time was 20 to 43 minutes, with an average of 26.59 ± 6.18 minutes with no intraoperative complications. The follow-up duration ranged from 1 to 12 months (mean = 5.28 ± 3.07) and the follow-up rate was 100%. The rate of postoperative complications was 4.55% (4/88), including port-site infection in two cases, fibrin sheath formation in one case, and port flip in one case. No other complications were observed during follow-up.

Conclusion:

Ultrasound-guided TIVAP implantation via the posterior approach of the IJV is feasible, safe, and effective, with a low rate of intraoperative and postoperative complications. Not only was the curvature of the catheter device smooth, but patients were satisfied with the comfort and cosmetic appearance. Additionally, we could reduce the possible complications of pinching and kinking of the catheter by using this approach. Therefore, further large-sample, prospective, and randomized controlled trials are warranted.
Leber’s hereditary optic neuropathy: Update on the novel genes and therapeutic options
Authors: Hu Jui-Lin , Hsu Chih-Chien , Hsiao Yu-Jer , Lin Yi-Ying , Lai Wei-Yi , Liu Yu-Hao , Wang Chia-Lin , Ko Yu-Ling , Tsai Ming-Long , Tseng Huan-Chin , Chien Yueh , Yang Yi-Ping
Published: November 2023

A maternal inheritance disorder called Leber’s hereditary optic neuropathy (LHON) is the most common primary mitochondrial deoxyribonucleic acid (DNA) disorder. In most studies, there are more male patients than female patients, which contradicts the usual pattern in mitochondrial hereditary diseases. This suggests that nuclear DNA (nDNA) may influence the degeneration of retinal ganglion cells (RGCs) in LHON. The primary cause of this is dysfunction in complex I of the electron transport chain, leading to ineffective adenosine triphosphate (ATP) production. In addition to MT-ND4 or MT-ND1 mutations, genes such as PRICKLE3, YARS2, and DNAJC30, which come from nDNA, also play a role in LHON. These three genes affect the electron chain transport differently. PRICKLE3 interacts with ATP synthase (complex V) at Xp11.23, while YARS2 is a tyrosyl-tRNA synthetase 2 involved in mitochondria. DNAJC30 mutations result in autosomal recessive LHON (arLHON). Understanding how genes impact the disease is crucial for developing new treatments. Idebenone has been approved for treating LHON and has shown safety and efficacy in clinical trials. Mesenchymal stem cell-based therapy has also emerged as a potential treatment for LHON by transferring mitochondria into target cells. Gene therapy research focuses on specific gene mutations, and the wild-type ND4 gene target in the adeno-associated viruses (AAV) vector has shown promise in clinical trials as a potential treatment for LHON.
Knowing the Patient
Authors: Marzinski Sara , Melrose Diane , Moynihan Therese , Hlebichuk Jeanne , Liao Yunqi , Hook Mary
Published: November 2023

Background

Heart failure (HF) is a complex problem characterized by frequent hospitalizations and high 30-day readmission rates. Researchers studying HF readmission report that patients and clinicians have different perspectives on readmission and preventability when unadjusted for disease severity.

Objective

The aim of this study was to gather patient, caregiver, nurse, and physician subjective reason(s) for 30-day HF readmission and perceptions of preventability with contextual factors to evaluate differences.

Methods

A convergent, parallel, mixed-methods design was used with interviews and chart reviews to evaluate contextual factors from the current and index hospital stay. Adults readmitted within 30 days of a previous inpatient stay with a coded HF diagnosis were enrolled and interviewed, followed by interviews with associated caregivers, attending physicians, and assigned nurses.

Results

Interviews were conducted with patients (n = 44), caregivers (n = 6), physicians (n = 24), and nurses (n = 44). Readmissions were emergent/urgent (95%) and occurred within 14.9 days (SD, 8.1; 2–28 days) on average after discharge. Index stay coding revealed that most patients (73%) had a high severity of illness (73%) and risk of mortality (68%). Heart failure stage was inconsistently documented. Patients reported acute symptomatic reasons, with only 32% describing readmission as preventable. Physicians reported diagnostic reasons, 38% of which were preventable. Nurses reported behavioral reasons, with 59% being preventable. Patient/clinician agreement on readmission reason was low (30%).

Conclusions

Patient/clinician perspectives on readmission varied among the patients with complex HF. Care planning based on HF stage and other contextual factors is needed to ensure a shared understanding of disease severity and a tailored symptom management approach to prevent readmission.
The causal relationship between depression and frozen shoulder: A two-sample Mendelian randomization
Authors: Deng Guang-hua , Wei Yong-kang
Published: November 2023

To investigate the causal relationship between depression and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with depression and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between depression and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results showed an odds ratio (95% confidence interval) of 1.18 (0.91–1.53), P = .204, indicating that depression was not causally related to the development of frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using a two-sample MR analysis, and the results showed no causal relationship between depression and the occurrence of frozen shoulder, requiring the inclusion of a larger sample for the study.
Frontiers in chronic fatigue syndrome research: An analysis of the top 100 most influential articles in the field
Authors: Wang Xingxin , Li Xuhao , Dong Tiantian , Yu Wenyan , Jia Zhixia , Chen Jun
Published: November 2023

Chronic fatigue syndrome (CFS) is a complex constellation of symptoms that significantly reduces the quality of life among affected individuals and increases public health expenditures. We conducted a search on the Web of Science Core Collection database and selected the top 100 cited articles in the field of CFS. Several literature analysis tools, including CiteSpace 6.1.R6, VOSviewer 1.6.19, and Scimago Graphica 1.0.30, were utilized to integrate the most influential research papers and academic journals in order to obtain a comprehensive understanding of the CFS field. The top 100 highly-cited publications were published in 67 reputable journals, with contributions from 250 institutions across 26 countries/regions involved in CFS research. This demonstrates the extensive attention and coverage of CFS research by high-quality academic journals and institutions, highlighting the interdisciplinary and multidisciplinary nature of CFS studies. The journal with the highest publication volume and total citations was Lancet. The top 5 co-occurring keywords were chronic fatigue syndrome, cognitive behavior therapy, epidemiology, definition, and disorders, indicating the ongoing attention researchers have devoted to the diagnostic criteria and clinical studies of CFS. Cluster analysis results suggested that primary care, infectious retrovirus, gene expression, and metabolomics may become the focal points and trends in future CFS research. The prospective research directions in this field include the search for biological markers, with a particular focus on immunology; the advancement of diagnostic techniques; the screening of risk genes associated with CFS; and the conduct of epidemiological investigations.
Lymphoma of the central nervous system originating from the septum pellucidum region: Two case reports with literature review
Authors: Chen Dawei , Yan Xu , Lu Liuzhe , Xue Kun , Dong Xuechao
Published: November 2023

Rationale:

Non-Hodgkin lymphoma affecting the brain, eyes, and cerebrospinal fluid without systemic spread is known as primary central nervous system lymphoma (PCNSL). While intracerebroventricular PCNSL is commonly found in the lateral ventricles and the third and fourth ventricles, the occurrence of PCNSL originating from the septum pellucidum is extremely rare.

Patient Concerns:

Two patients presented with recent memory loss and high cranial pressure.

Diagnoses:

Magnetic resonance imaging revealed a clear enhancing lesion in the septum pellucidum region. Pathological examination confirmed that both cases were primary large B-cell lymphoma GCB (germinal center B-cell-like) subtypes located in an “immune-privileged” area.

Interventions:

Both patients underwent total tumor resection, and the procedures were successfully completed without surgical complications.

Outcomes:

Over a 1-year period, treatment included four cycles of high-dose methotrexate combined with temozolomide. During the follow-up period (19–23 months), no recurrence of the lymphoma was observed.

Lessons:

In cases of PCNSL in the septum pellucidum, it is crucial to consider it as a potential differential diagnosis for intraventricular tumors. Surgical interventions should focus on maximizing tumor resection while ensuring the protection of critical structures like the fornix and peripheral neural components. The role of surgery compared to biopsy, as well as the long-term complications, necessitates extended follow-up. Additionally, an individualized treatment approach, considering factors such as age, Karnofsky performance score, and organ function assessment, can lead to positive outcomes.
Application of platelet-rich-plasma in the postoperative treatment of perianal abscess pseudohealing: A case report
Authors: Liang Shuang , Ma Weijuan , Jia Sihui , Zhao Gang , Li Ying , Li Yaxin , Wang Licun , Liu Zheng , Liu Jiao , Gao Hairui , Wang Haiyan
Published: November 2023

Rationale:

Perianal abscess is a common disease of the anus and intestine. Surgery is an important treatment option for perianal abscess. However, some patients have a long healing time, poor healing effect after surgery, or even pseudo-healing. Platelet-rich plasma (PRP) is rich in platelets that can release a large number of factors when activated and promote wound healing. Moreover, there are few reports on the use of PRP for wounds that are difficult to heal after perianal abscess surgery.

Patient concerns:

The patient had reported a complaint of perianal swelling and discomfort associated with anal pain, which was considered a perianal abscess. Ceftriaxone, fumigation, and sitz bath were administered after mixed hemorrhoid and perianal abscess surgeries were performed; however, the wound remained unhealed for more than 3 months, and there was a fistula under the skin.

Diagnosis:

Perianal color ultrasonography revealed perianal abscess.

Interventions:

Autologous PRP treatment was performed 5 times for each patient.

Outcomes:

The postoperative wound healed within 15 days after 5 times PRP treatments.

Lessons:

PRP is a novel treatment option for pseudo-healing.
Network pharmacology and molecular docking study on the treatment of polycystic ovary syndrome with angelica sinensis- radix rehmanniae drug pair
Authors: Li Xinghua , Ullah Ihsan , Hou Chunxia , Liu Yuqiang , Xiao Keyuan
Published: November 2023

This study aimed to investigate theangelica sinensis-radix rehmanniae(AR) role in polycystic ovary syndrome (PCOS), employing network pharmacology and molecular docking techniques for active ingredient, targets, and pathway prediction. AR active components were obtained through TCMSP platform and literature search. The related targets of AR and PCOS were obtained through the disease and Swiss Target Prediction databases. An “active ingredient-target” network map was constructed using Cytoscape software, and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis was conducted through Hiplot. Finally, Auto Dock Tools software was used to conduct molecular docking between active ingredients and core targets. The main bioactive ingredients of AR in the treatment of PCOS are acteoside, baicalin, caffeic acid, cistanoside F, geniposide, etc. These ingredients involve 10 core targets, such as SRC, HSP90AA1, STAT3, MAPK1, and JUN. The effect of AR on anti-PCOS mainly involves the AGE-RAGE signaling pathway, Relaxin signaling pathway, TNF signaling pathway, and ErbB signaling pathway. Molecular docking results showed that the main active components and key targets of AR could be stably combined. AR can improve hyperandrogen status, regulate glucose homeostasis, and correct lipid metabolism and other physiological processes through multi-component, multi-target, and multi-pathway. Thus, it could play a significant role in PCOS treatment. The results of our study provide a scientific foundation for basic research and clinical applications of AR for the treatment of PCOS.
Regulations of malaria in children with human immunodeficiency virus infection: A review
Authors: Opeyemi Abdulrahman Abdulbasit , Obeagu Emmanuel Ifeanyi
Published: November 2023

This comprehensive review explores the intricate relationship between 2 major global health challenges, malaria and HIV, with a specific focus on their impact on children. These diseases, both endemic in sub-Saharan Africa, create a dual burden that significantly elevates the risk of morbidity and mortality, particularly in children with compromised immune systems due to HIV. The review delves into the complex mechanisms by which these infections interact, from heightened clinical malaria frequencies in HIV-infected individuals to the potential impact of antiretroviral therapy on malaria treatment. Different research engines were utilized in writing this paper such as Web of Science, Google Scholar, Pubmed Central, ResearchGate, and Academia Edu. To address this critical health concern, the study identifies and discusses various regulatory and treatment strategies. It emphasizes the importance of daily cotrimoxazole prophylaxis and insecticide-treated nets in preventing malaria in children with HIV. The potential of antiretroviral protease inhibitors and mRNA-based vaccines as innovative solutions is highlighted. Additionally, the study underscores the significance of climate data and artificial intelligence in improving diagnostics and drug development. Furthermore, the review introduces the concept of genetically modified mosquitoes as a novel approach to vector control, offering a promising avenue to protect HIV-positive individuals from mosquito-borne diseases like malaria. Through a comprehensive analysis of these strategies, the study aims to provide a foundation for policymakers, healthcare professionals, and researchers to develop effective regulations and interventions that reduce the dual burden of malaria and HIV in children, improving public health outcomes in endemic regions.
Effective Care Transitions
Authors: Kinard Tara , Brennan-Cook Jill , Johnson Sara , Long Andrea , Yeatts John , Halpern David
Published: November 2023

Purpose/Objectives:

Care transitions from one setting to another are vulnerable spaces where patients are susceptible to complications. Health systems, accountable care organizations, and payers recognize that care transition interventions are necessary to reduce unnecessary cost and utilization and improve patient outcomes following a hospitalization. Multiple care transition models exist, with varying degrees of intensity and success. This article describes a quality improvement project for a care transition model that incorporates key elements from the American Case Management Association's Transitions of Care Standards and the Transitional Care Management services as outlined by the Centers for Medicare & Medicaid Services.

Primary Practice Setting:

A collaboratively developed care transition model was implemented between a health system population health management office and a primary care organization.

Findings/Conclusions:

An effective care transitions model is stronger with collaboration among core members of a patient's care team, including a nurse care manager and a primary care provider. Ongoing quality improvement is necessary to gain efficiencies and effectiveness of such a model.

Implications for Case Management Practice:

Care managers are integral in coordinating effective transitions. Care management practice includes transition of care standards that are associated with improved outcomes for patients at high risk for readmission. Interventions inclusive of medication reconciliation, identification and addressing of health-related social needs, review of discharge instructions, and coordinated follow-up are important factors that impact patient outcomes. Patients and their health system care teams benefit from the role of a care manager when there is a collaborative, coordinated, and timely approach to hospital follow-up.
Growth of Remote Therapeutic Monitoring Lands New Opportunities for Case Management
Authors: Moreo Kathleen , Sapir Tamar
Published: November 2023

Purpose/Objectives:

An increase in the use of remote therapeutic monitoring (RTM) has been spurred by nationwide factors including the COVID-19 pandemic, authorized reimbursement of RTM by the Centers for Medicare & Medicaid Services, and more frequent use of big data analytics in health care delivery. This article discusses the use of RTM by care teams at the point of care and explores the role of the case manager in RTM to address patients' unmet needs.

Primary Practice Settings:

Although RTM may be utilized across inpatient and outpatient levels of care, this article focuses on outpatient care such as community clinics, provider groups, and home health care.

Findings/Conclusions:

When implemented along with care management interventions, RTM applications have the potential to improve patient adherence, enhance communication between patients and their providers, streamline resource allocation, and address social determinants of health impacting patient care and outcomes.

Implications for Case Management Practice:

RTM reimbursement models are rapidly evolving, utilizing real-world and patient-reported data to identify and initiate timely, individualized solutions that meet the holistic needs of each patient. Use of an RTM system allows the case manager to build rapport with the patient while quickly identifying care gaps and delivering appropriate interventions that can maximize patient outcomes. RTM can drive savings and bring revenue to the system or practice while providing salient documentation of social determinants of health that can be addressed with validation of proven care coordination interventions.
Post–Face Lift Facial Paralysis: A 20-Year Experience
Authors: Kaufman Goldberg Tal , McGonagle Elizabeth R. , Hadlock Tessa A.
Published: November 2023

Background:

Facial nerve (FN) injury during a face lift is a relatively rare but potentially devastating complication. Despite extensive literature discussing FN anatomy and danger zones, few studies describe detailed management, FN exploration intraoperative findings, and outcome after post–face lift facial paralysis (PFFP). The authors reviewed a 20-year experience in managing iatrogenic PFFP.

Methods:

Patients with PFFP were retrospectively identified between 2002 and 2022. Demographic data, operative details from the face lift procedure, facial function after face lift, medical and surgical management, intraoperative findings, and long-term outcomes were analyzed.

Results:

A total of 25 patients who experienced PFFP were referred for evaluation over the past 20 years. Eight patients required FN exploration, 6 of whom underwent nerve repair; all recovered to some degree, with 50% achieving essentially normal facial function. Fourteen patients underwent nonsurgical management, including physical therapy, chemodenervation, and filler therapy. Of these nonsurgical patients who were not lost to follow-up, 50% achieved normal facial function and 42% achieved nearly normal facial function. The single patient who had no spontaneous improvement presented outside the reinnervation window and was not an operative candidate.

Conclusions:

PFFP outcome depends on injury type and location, accurate assessment, and appropriate treatment; however, the overall prognosis is favorable. FN exploration is warranted when nerve transection is suspected. Observation is suitable for patients demonstrating early signs of recovery. Patients presenting beyond a reasonable reinnervation window will need other facial reanimation techniques. When FN exploration is required, outcomes may be superior in a facial nerve center setting. Adjunctive interventions for symmetry improvement while awaiting recovery are available.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Determining Degree of Hypertrophy and Extent of Resection in Aesthetic Labia Minora Reduction: Technical Highlights and Step-by-Step Video Guide
Authors: Munhoz Alexandre Mendonça , Marques Neto Ary de Azevedo
Published: November 2023

Advances in aesthetic labia minora (LM) procedures have led to better results and fewer complications. Edge trim or wedge approaches are used, both of which use hidden incisions and preserve the edges of the LM. Since 1998, we have been performing a simple and reliable technique based on inferior wedge LM resection and superior pedicle flap reconstruction. Although details of aesthetic LM reduction have been amply published, previous technical videos have not presented a detailed step-by-step description, and few studies specifically address how to estimate the amount of tissue to resect according to the degree of hypertrophy. This article and the accompanying videos provide a detailed guide that clearly outlines the senior author’s (A.M.M.) technique for aesthetic LM reduction. The authors’ experience demonstrates that superior pedicle flap reconstruction is a reliable and reproducible technique. The success of the procedure depends on patient selection, careful preoperative planning, and adequate intraoperative management.
Primary HIV infection features colonic damage and neutrophil inflammation yet containment of microbial translocation
Authors: Tincati Camilla , Bono Valeria , Cannizzo Elvira Stefania , Tosi Delfina , Savi Federica , Falcinella Camilla , Casabianca Anna , Orlandi Chiara , Luigiano Carmelo , Augello Matteo , Rusconi Stefano , Muscatello Antonio , Bandera Alessandra , Calcagno Andrea , Gori Andrea , Nozza Silvia , Marchetti Giulia
Published: November 2023

Introduction:

Impairment of the gastrointestinal barrier leads to microbial translocation and peripheral immune activation, which are linked to disease progression. Data in the setting of primary HIV/SIV infection suggest that gut barrier damage is one of the first events of the pathogenic cascade, preceding mucosal immune dysfunction and microbial translocation. We assessed gut structure and immunity as well as microbial translocation in acutely and chronically-infected, combination antiretroviral therapy (cART)-naive individuals.

Methods:

Fifteen people with primary HIV infection (P-HIV) and 13 with chronic HIV infection (C-HIV) c-ART-naive participants were cross-sectionally studied. Gut biopsies were analysed in terms of gut reservoirs (total, integrated and unintegrated HIV DNA); tight junction proteins (E-cadherin, Zonula Occludens-1), CD4+ expression, neutrophil myeloperoxidase (histochemical staining); collagen deposition (Masson staining). Flow cytometry was used to assess γδ T-cell frequency (CD3+panγδ+Vδ1+/Vδ2+). In plasma, we measured microbial translocation (LPS, sCD14, EndoCAb) and gut barrier function (I-FABP) markers (ELISA).

Results:

P-HIV displayed significantly higher tissue HIV DNA, yet neutrophil infiltration and collagen deposition in the gut were similar in the two groups. In contrast, microbial translocation markers were significantly lower in P-HIV compared with C-HIV. A trend to higher mucosal E-cadherin, and gut γδ T-cells was also observed in P-HIV.

Conclusion:

Early HIV infection features higher HIV DNA in the gut, yet comparable mucosal alterations to those observed in chronic infection. In contrast, microbial translocation is contained in primary HIV infection, likely because of a partial preservation of E-cadherin and mucosal immune subsets, namely γδ T-cells.
Computed Tomography–Based Radiomics Signature for Predicting Segmental Chromosomal Aberrations at 1p36 and 11q23 in Pediatric Neuroblastoma
Authors: Wang Haoru , Yu Chunlin , Ding Hao , Zhang Li , Chen Xin , He Ling
Published: November 2023

Objective

This study aimed to develop and assess the precision of a radiomics signature based on computed tomography imaging for predicting segmental chromosomal aberrations (SCAs) status at 1p36 and 11q23 in neuroblastoma.

Methods

Eighty-seven pediatric patients diagnosed with neuroblastoma and with confirmed genetic testing for SCAs status at 1p36 and 11q23 were enrolled and randomly stratified into a training set and a test set. Radiomics features were extracted from 3-phase computed tomography images and analyzed using various statistical methods. An optimal set of radiomics features was selected using a least absolute shrinkage and selection operator regression model to calculate the radiomics score for each patient. The radiomics signature was validated using receiver operating characteristic curves to obtain the area under the curve and 95% confidence interval (CI).

Results

Eight radiomics features were carefully selected and used to compute the radiomics score, which demonstrated a statistically significant distinction between the SCAs and non-SCAs groups in both sets. The radiomics signature achieved an area under the curve of 0.869 (95% CI, 0.788–0.943) and 0.883 (95% CI, 0.753–0.978) in the training and test sets, respectively. The accuracy of the radiomics signature was 0.817 and 0.778 in the training and test sets, respectively. The Hosmer-Lemeshow test confirmed that the radiomics signature was well calibrated.

Conclusions

Computed tomography–based radiomics signature has the potential to predict SCAs at 1p36 and 11q23 in neuroblastoma.
Myocardial, Retro-orbital, and Bilateral Testicular Metastases of an Ileal Neuroendocrine Tumor in 68Ga-DOTATATE PET/CT
Authors: Rogeau Antoine , Kaplar Zoltan , Fraioli Francesco
Published: November 2023

A 71-year-old man with a newly discovered metastatic grade II neuroendocrine tumor of the terminal ileum was referred for a 68Ga-DOTATATE PET/CT scan to stage the disease and assess suitability for PRRT (peptide receptor radionuclide therapy). The patient was known to have secondary nodal and bone/liver metastatic disease through prior morphological investigations. PET images revealed an atypical pattern of metastatic disease, showcasing secondary lesions in bilateral extraocular muscles, the myocardium, and both testes. The patient was pauci-symptomatic and only reported fatigue and diarrhea. Management involved lanreotide administration, and PRRT is being envisaged.
In Vivo Analysis of Porous Bioactive Silicon Carbide Scaffold for Craniofacial Bone Augmentation
Authors: Alfotawi Randa , Premnath Sangeetha , El-Ghannam Ahmad , Alsafadi Mona , Mahmood Amer
Published: November 2023

Background:

Bone augmentation is a vital area of research because of its high clinical demand and the reported complications associated with the available biomaterials. Purpose: The study assess the role of decellurized skeletal muscle (DSM) when combined with synthesized porous bioactive silicon carbide (SiC) ceramic and evaluated its ability to augment bone calvaria in a rat model.

Material and Methods:

Eighteen rats were divided into 2 groups; group 1 (n=9), SiC discs (10 × 0.2 mm) pre-treated with 20% NaOH were placed as an onlay grafts on calvarial bone. Meanwhile, in group 2 (n=9), SiC discs pre-treated with 20% NaOH (10 × 0.2 mm) were covered with DSM. After 12 weeks, the grafted tissues were harvested and examined using cone-beam computed tomography, mechanical testing, and histologic analysis.

Results:

Cone-beam computed tomography for group 2 showed more radio-opacity for the remnant of SiC compared with native bone. The surface area and volume of radio-opacity were 2.48 mm2 ± 1.6 and 14.9 ± 7.8 mm3, respectively. The estimated quantitative average surface area of the radio-opacity for group 1 and volume were 2.55 mm2 ± (Sd=3.7) and 11.25 ± (Sd=8.9), respectively. Mechanically, comparable values of the flexural strength and statistically significant higher modulus of elasticity of calvaria in group 1 compared with group 2 and control (P<0.001). Histologically, group 2 region of woven bone was seen close to the lamellar bone (native bone), and there was immature bone present near the implanted SiC.

Conclusion:

The tested construct made of SiC/DSM has potential to osteointegrate into native bone, making it a suitable material for bone augmentation.
Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act
Authors: Motter Jennifer D. , Hussain Sarah , Brown Diane M. , Florman Sander , Rana Meenakshi M. , Friedman-Moraco Rachel , Gilbert Alexander J. , Stock Peter , Mehta Shikha , Mehta Sapna A. , Stosor Valentina , Elias Nahel , Pereira Marcus R. , Haidar Ghady , Malinis Maricar , Morris Michele I. , Hand Jonathan , Aslam Saima , Schaenman Joanna M. , Baddley John , Small Catherine B. , Wojciechowski David , Santos Carlos A.Q. , Blumberg Emily A. , Odim Jonah , Apewokin Senu K. , Giorgakis Emmanouil , Bowring Mary Grace , Werbel William A. , Desai Niraj M. , Tobian Aaron A.R. , Segev Dorry L. , Massie Allan B. , Durand Christine M. ,   on behalf of the HOPE in Action Investigators
Published: November 2023

Background.

Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D+), it is crucial to understand whether this has impacted transplant rates for this population.

Methods.

Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D+ kidneys (HOPE) compared with 46 025 candidates not listed for D+ kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D+, false-positive [FP; donor with false-positive HIV testing], D– [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure.

Results.

HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D+, 34% D–, 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D–, 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates (P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001).

Conclusions.

Listing for D+ kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.
SARS-CoV-2 Variants Omicron BA.4/5 and XBB.1.5 Significantly Escape T Cell Recognition in Solid-organ Transplant Recipients Vaccinated Against the Ancestral Strain
Authors: Halvorson Torin , Ivison Sabine , Huang Qing , Ladua Gale , Yotis Demitra M. , Mannar Dhiraj , Subramaniam Sriram , Ferreira Victor H. , Kumar Deepali , Belga Sara , Levings Megan K. ,   on behalf of the PREVenT Study Group
Published: November 2023

Background.

Immune-suppressed solid-organ transplant recipients (SOTRs) display impaired humoral responses to COVID-19 vaccination, but T cell responses are incompletely understood. SARS-CoV-2 variants Omicron BA.4/5 (BA.4/5) and XBB.1.5 escape neutralization by antibodies induced by vaccination or infection with earlier strains, but T cell recognition of these lineages in SOTRs is unclear.

Methods.

We characterized Spike-specific T cell responses to ancestral SARS-CoV-2 and BA.4/5 peptides in 42 kidney, liver, and lung transplant recipients throughout a 3- or 4-dose ancestral Spike mRNA vaccination schedule. As the XBB.1.5 variant emerged during the study, we tested vaccine-induced T cell responses in 10 additional participants using recombinant XBB.1.5 Spike protein. Using an optimized activation-induced marker assay, we quantified circulating Spike-specific CD4+ and CD8+ T cells based on antigen-stimulated expression of CD134, CD69, CD25, CD137, and/or CD107a.

Results.

Vaccination strongly induced SARS-CoV-2-specific T cells, including BA.4/5- and XBB.1.5-reactive T cells, which remained detectable over time and further increased following a fourth dose. However, responses to BA.4/5 (1.34- to 1.67-fold lower) XBB.1.5 (2.0- to 18-fold lower) were significantly reduced in magnitude compared with ancestral strain responses. CD4+ responses correlated with anti-receptor-binding domain antibodies and predicted subsequent antibody responses in seronegative individuals. Lung transplant recipients receiving prednisone and older adults displayed weaker responses.

Conclusions.

Ancestral strain vaccination stimulates BA.4/5 and XBB.1.5-cross-reactive T cells in SOTRs, but at lower magnitudes. Antigen-specific T cells can predict future antibody responses. Our data support monitoring both humoral and cellular immunity in SOTRs to track COVID-19 vaccine immunogenicity against emerging variants.
Genotypic Characterization of Urinary Tract Infections causing bacteria isolates among Adults at Kiambu Level 5 Hospital, Kenya: Selected Extended Spectrum β-Lactamase genes and Biofilm Formation
Authors: Wanja Fredrick K. , Omwenga Eric O. , Ngugi Caroline W. , Maina John N. , Kiiru John N.
Published: November 2023

The menace of antimicrobial resistance to public health is constantly arising globally. Many pathogenic bacteria use mechanisms such as mutations and biofilm formation, significantly reducing antimicrobial agents' efficacy. In this cross-sectional study, we aimed to determine the prevalence of selected extended spectrum β-lactamase (ESβLs) genes and analyse the biofilm formation abilities of the isolated bacteria causing urinary tract infection among adult patients against selected drug dosages seeking Medicare at Kiambu Level 5 Hospital, Kenya. The double-disk synergy test was used for phenotypic identification of ESβLs producing isolates, while microtiter plate assays with some modifications were used for the biofilm formation test. A total of 10 isolates were bioassayed for ESβL genes presence out of 57 bacteria isolates obtained from urine samples. This study found the blaTEM genes to be the most prevalent ESβLs type 10/10 (100%), followed by blaOXA and blaSHV genes at 4/10 (40%) and 3/10 (30%), respectively. In addition, the co-carriage of blaTEM and blaSHV was 50% lower than that of blaTEM + blaOXA genes at 66.7% among the study Escherichia coli isolates. Biofilm formation was positive in 36/57 (63.2%) of the isolates tested, with most being Gram-negative 25/36 (69.4%). Escherichia coli 15/36 (41.7 %), Klebsiella species 7/36 (19.4%), and Staphylococcus aureus 7/36 (19.4%) were the dominant biofilm formers. However, there was no significant difference in biofilm formation among all tested isolates, with all isolates recording p-values above 0.05. In light of these findings, biofilm formation potential coupled with antimicrobial resistance genes in UTI isolates could likely lead to difficult to treat infections.
Empedobacter sedimenti sp. nov., isolated from sediment of East Taihu Lake
Authors: Ruan Luyao , Liu Le , Jiang Xueting , Mao Dongmei , Shao Jiahui , He Jian , Shen Qirong
Published: November 2023

A Gram-reaction-negative, strictly aerobic, pale yellow, non-gliding, rod-shaped bacterium, designated DT-LB-19T, was isolated from the sediment of East Taihu Lake in Jiangsu Province, PR China. Strain DT-LB-19T showed the highest 16S rRNA gene sequence similarities to members of the genera

Algoriella

,

Chishuiella

and

Empedobacter

(94.84–95.77 %) in the family

Weeksellaceae

. In phylogenetic trees based on genomes, strain DT-LB-19T clustered within the genus

Empedobacter

but formed a separate subclade with a high bootstrap value. The average nucleotide identity and digital DNA–DNA hybridization values between DT-LB-19T and the closely related type strains were in the range of 82.5–86.9 % and 25.8–32.3 %, respectively. The major cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 1
 ω5c, C16 : 0, summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B), summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and iso-C15 : 03-OH. The predominant menaquinone was menaquinone-6. The polar lipid profile consisted of phosphatidylethanolamine, one glycolipid, two aminophospholipids and five unidentified lipids. The DNA G+C content was 31.8 mol%. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic results, we propose that strain DT-LB-19T represents a novel species of the genus

Empedobacter

, for which the name Empedobacter sedimenti sp. nov. is proposed, with strain DT-LB-19T (=KCTC 82330T=CCTCC AB 2023026T= JSACC 11448T) as the type strain.
Molecular and biological characterization of a partitivirus from Paecilomyces variotii
Authors: Hassan Sidra , Syun-ichi Urayama , Shabeer Saba , Wu Chien-Fu , Moriyama Hiromitsu , Coutts Robert H. A. , Kotta-Loizou Ioly , Jamal Atif
Published: November 2023

Paeciliomyces variotii is a thermo-tolerant, ubiquitous fungus commonly found in food products, indoor environments, soil and clinical samples. It is a well-known biocontrol agent used against phytopathogenic fungi and its metabolites have many industrial applications. Rare reports of P. variotii-related human infections have been found in the medical literature. In this study, we report for the first time the infection of P. variotii isolated from a soil sample collected in a rice field with a double-stranded RNA virus, Paeciliomyces variotii partitivirus 1 (PvPV-1) in the family Partitiviridae. P. variotii harboured icosahedral virus particles 30 nm in diameter with two dsRNA segments 1758 and 1356 bp long. Both dsRNA1 and dsRNA2 have a single open reading frame encoding proteins of 63 and 40 kDa, respectively. These proteins have significant similarity to the RNA-dependent RNA polymerase and capsid protein encoded by the genomic segments of several viruses from the family Partitiviridae. Phylogenetic analysis revealed that PvPV-1 belongs to the family Partitiviridae but in an unclassified group/genus, tentatively nominated Zetapartitivirus. PvPV-1 was found to increase the growth rate of the host fungus, as indicated by time course experiments performed on a range of different media for virus-infected and virus-free isogenic lines. Further, dual-culture assays performed for both isogenic lines confirmed the antagonistic potential of P. variotii against other phytopathogenic fungi. The findings of this study assist us in understanding P. variotii as a potential biocontrol agent, together with plant–fungus–virus interactions.
Saliva sampling and its direct lysis is an excellent option for SARS-CoV-2 diagnosis in paediatric patients: comparison with the PanBio COVID-19 antigen rapid test in symptomatic and asymptomatic children
Authors: Moreno-Contreras Joaquín , Espinoza Marco A. , Cantú-Cuevas Marco A. , Madrid-González Daniel A. , Barón-Olivares Héctor , Ortiz-Orozco Oscar D. , Guzmán-Rodríguez Cecilia , Arias Carlos F. , Lopez Susana
Published: November 2023

Introduction. Lateral flow test (LFTs) have been used as an alternative to reverse transcription quantitative PCR (RT-qPCR) in point-of-care testing. Despite their benefits, the sensitivity of LFTs may be low and is affected by several factors. We have previously reported the feasibility of using direct lysis of individual or pools of saliva samples from symptomatic and asymptomatic patients as a source of viral genomes for detection by RT-qPCR.

Hypothesis. Direct lysed saliva is more sensitive than antigen tests to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in samples from children.

Aim. Our goals here were to valuate the specificity and sensitivity of the PanBio COVID-19 antigen rapid test device (Ag-RTD) compared with RT-qPCR of direct lysed saliva.

Methodology. We evaluated the performance of the PanBio COVID-19 Ag-RTD in comparison to RT-qPCR direct lysed saliva from paired samples of 256 symptomatic and 242 asymptomatic paediatric patients.

Results. Overall, although there were no differences in the specificity (96.6%), we found a lower sensitivity (64.3%) of the PanBio Ag-test RTD compared to saliva in both symptomatic and asymptomatic patients. In addition, the sensitivity of PanBio was not correlated with the viral load present in the samples.

Conclusion. Our data highlight the benefits of using RT-qPCR and saliva samples for SARS-CoV-2 detection, particularly in paediatric patients.
Protection of β cells against pro-inflammatory cytokine stress by the GDF15-ERBB2 signaling
Authors: Sarkar Soumyadeep , Syed Farooq , Webb-Robertson Bobbie-Jo , Melchior John T. , Chang Garrick , Gritsenko Marina , Wang Yi-Ting , Tsai Chia-Feng , Liu Jing , Yi Xiaoyan , Cui Yi , Eizirik Decio L. , Metz Thomas O. , Rewers Marian , Evans-Molina Carmella , Mirmira Raghavendra G. , Nakayasu Ernesto S.
Published: November 2023

Aim/hypothesis

Growth/differentiation factor 15 (GDF15) is a therapeutic target for a variety of metabolic diseases, including type 1 diabetes (T1D). However, the nausea caused by GDF15 is a challenging point for therapeutic development. In addition, it is unknown why the endogenous GDF15 fails to protect from T1D development. Here, we investigate the GDF15 signaling in pancreatic islets towards opening possibilities for therapeutic targeting in β cells and to understand why this protection fails to occur naturally.

Methods

GDF15 signaling in islets was determined by proximity-ligation assay, untargeted proteomics, pathway analysis, and treatment of cells with specific inhibitors. To determine if GDF15 levels would increase prior to disease onset, plasma levels of GDF15 were measured in a longitudinal prospective study of children during T1D development (n=132 cases vs. n=40 controls) and in children with islet autoimmunity but normoglycemia (n=47 cases vs. n=40 controls) using targeted mass spectrometry. We also investigated the regulation of GDF15 production in islets by fluorescence microscopy and western blot analysis.

Results

The proximity-ligation assay identified ERBB2 as the GDF15 receptor in islets, which was confirmed using its specific antagonist, tucatinib. The untargeted proteomics analysis and caspase assay showed that ERBB2 activation by GDF15 reduces β cell apoptosis by downregulating caspase 8. In plasma, GDF15 levels were higher (p=0.0024) during T1D development compared to controls, but not in islet autoimmunity with normoglycemia. However, in the pancreatic islets GDF15 was depleted via sequestration of its mRNA into stress granules, resulting in translation halting.

Conclusions/interpretation

GDF15 protects against T1D via ERBB2-mediated decrease of caspase 8 expression in pancreatic islets. Circulating levels of GDF15 increases pre-T1D onset, which is insufficient to promote protection due to its localized depletion in the islets. These findings open opportunities for targeting GDF15 downstream signaling for pancreatic β cell protection in T1D and help to explain the lack of natural protection by the endogenous protein.
Computation on demand: Action-specific representations of visual task features arise during distinct movement phases
Authors: Lee Nina , Guo Lin Lawrence , Nestor Adrian , Niemeier Matthias
Published: November 2023

It is commonly held that computations of goal-directed behaviour are governed by conjunctive neural representations of the task features. However, support for this view comes from paradigms with arbitrary combinations of task features and task affordances that require representations in working memory. Therefore, in the present study we used a task that is well-rehearsed with task features that afford minimal working memory representations to investigate the temporal evolution of feature representations and their potential integration in the brain. Specifically, we recorded electroencephalography data from human participants while they first viewed and then grasped objects or touched them with a knuckle. Objects had different shapes and were made of heavy or light materials with shape and weight being features relevant for grasping but not for knuckling. Using multivariate analysis, we found that representations of object shape were similar for grasping and knuckling. However, only for grasping did early shape representations reactivate at later phases of grasp planning, suggesting that sensorimotor control signals feed back to early visual cortex. Grasp-specific representations of material/weight only arose during grasp execution after object contact during the load phase. A trend for integrated representations of shape and material also became grasp-specific but only briefly during movement onset. These results argue against the view that goal-directed actions inevitably join all features of a task into a sustained and unified neural representation. Instead, our results suggest that the brain generates action-specific representations of relevant features as required for the different subcomponent of its action computations.

Significance statement

The idea that all the features of a task are integrated into a joint representation or event file is widely supported but importantly based on paradigms with arbitrary stimulus-response combinations. Our study is the first to investigate grasping using electroencephalography to search for the neural basis of feature integration in such a daily-life task with overlearned stimulus-response mappings. Contrary to the notion of event files we find limited evidence for integrated representations. Instead, we find that task-relevant features form representations at specific phases of the action. Our results show that integrated representations do not occur universally for any kind of goal-directed behaviour but in a manner of computation on demand.