bluuebunny/crossref_metadata_2025 huggingface dataset:
Myopic shift after primary intraocular lens implantation in unilateral cataract children and its association with preoperative ocular parameters
Authors: Li Yunqian , Jin Guangming , Tan Yuan , Chen Hui , Jin Jiaxin , Luo Lixia , Chen Weirong , Lin Haotian , Liu Yizhi , Liu Zhenzhen
Published: September 2024

Purpose:

To assess the myopic shift in children with unilateral cataract undergoing primary intraocular lens (IOL) implantation and its association with preoperative ocular parameters.

Setting:

Single center.

Design:

Retrospective study.

Methods:

Children who underwent unilateral primary IOL implantation and were followed up for 3 years were included. Myopic shift and preoperative ocular parameters were compared between the treated and fellow eyes. The correlation between myopic shift and ocular parameters was assessed using partial correlation analysis. Potential factors influencing myopic shift were determined using linear regression analysis.

Results:

A total of 126 patients (252 eyes) were included. Longer preoperative axial length (AL) and steeper average keratometry (AK) in the treated eyes were noted in the whole cohort and patients aged 2 to <4 years (all P < .05). At 3 years postoperatively, mean myopic shift ranged from 3.53 diopters for children aged 1 to <2 years to 1.99 diopters for those aged 6 years and older. A greater myopic shift in the treated eyes was found in all, except children aged 6 years and older (P > .05). Preoperative interocular AL difference (IALD) was negatively correlated with myopic shift (r = 0.32, P < .001). Regression analysis revealed that younger age and smaller IALD were associated with greater myopic shift (P < .001 and P = .001, respectively).

Conclusions:

A greater myopic shift was observed in children with younger age at surgery and smaller IALD. To mitigate long-term anisometropia, selecting target refraction for unilateral pediatric cataracts should consider children's age, refractions of the fellow eyes, and preoperative IALD.
Sex-dependent effects of the targeted nerve growth factor mutation (R100E) on pain behavior, joint inflammation, and bone erosion in mice
Authors: Morado-Urbina Carlos E. , Kato Jungo , Sandor Katalin , Vazquez-Mora Juan Antonio , Ängeby Möller Kristina , Simon Nils , Salcido Jaira , Martinez-Martinez Arisai , Munoz-Islas Enriqueta , Jimenez-Andrade Juan Miguel , Svensson Camilla I.
Published: September 2024

Nerve growth factor (NGF)-R100E is a mutated form of human recombinant NGF that reduces the binding of NGF to its p75NTR receptor while retaining its affinity toward the TrkA receptor. Here, we used human wild type NGF and NGF-R100E knock-in mice to investigate the effects of this NGF mutation on inflammation-induced pain-related behaviors and bone loss. The hNGF-R100E mutation did not alter the nerve fiber density in the sciatic nerve, ankle joint synovium, and skin of naïve mice. Withdrawal responses to mechanical, thermal, and cold stimuli before and after joint inflammation induced by intra-articular injection of complete Freund adjuvant (CFA) were similar between human recombinant nerve growth factor-wild type and hNGF-R100E male and female mice while weight bearing and gait analysis revealed significant differences. Intriguingly, hNGF-R100E male and female mice showed only mild changes, indicating lower degrees of deep joint–related pain compared to their wild type counterparts. Furthermore, micro-CT analysis demonstrated that hNGF-R100E female mice, but not males, were protected from CFA-induced bone loss, and mRNA analysis showed a different gene regulation indicating a sex-dependent relationship between NGF, inflammation, and bone loss. In conclusion, our study reveals that the hNGF-R100E mutation renders mice insensitive to inflammation-induced impact on joint loading and gait while preserving the development of the peripheral nociceptive neurons and sensitivity to punctate stimulation of the skin. Notably, the mutation uncovers a sex-dependent relationship between NGF and inflammation-induced bone loss. These findings offer valuable insights into NGF as a target for pain management and the interplay between NGF and bone architecture.
Autonomy and Respect in Pregnancy Care for LGBTQIA+ Families
Authors: Faulk Karen Ann , Carroll Mary , Niemczyk Nancy , Braxter Betty
Published: September 2024

The purpose of this program evaluation was to gather information on proportions of LGBTQIA+ individuals and families, their needs, and care experiences in a county health department’s home visiting programs for perinatal clients and to make recommendations for improving culturally competent care for LGBTQIA+ individuals and families. In this engaged scholarship partnership, home visiting nurses administered a questionnaire to perinatal clients including demographic information on sexual orientation and gender identity. Differences between LBGTQIA+ identifying individuals’ perception of the perinatal care received and those of heterosexual, cisgender individuals were assessed. On the basis of these data, 10% of the 52 respondents identified as LGBTQIA+ and 4% identified with a gender other than “woman.” Clients who identified as straight had similar mean scores to those who listed an LGBTQIA+ sexual orientation. Clients who chose a gender identity other than “woman” had scores that fell within the 50th to 75th percentile of the overall mean. Qualitative interviews with 2 respondents provided additional in-depth information on their experiences. Overall, clients served by these perinatal programs reported similar diversity in terms of gender identity and sexual orientation as compared with national averages. This project provided evidence of the diversity among the clientele served by this agency and the importance of expanding the focus on inclusionary language and practices.
Introducing a Resource to Support Neonatal Nurse Engagement in Clinical Research©
Authors: Short Mary A.
Published: September 2024

Purpose:

This paper introduces the Resource to Support Neonatal Nurse Engagement in Clinical Research© to educate and support engagement of nurses in study design and protocol review. The resource serves to promote collaboration between nurses and pharmaceutical researchers to advance the development of neonatal therapies.

Background:

Neonates remain therapeutic orphans, underserved by the drug development community. Off-label use of drugs in neonates negatively impacts the evaluation of their safety and efficacy. Although NICU nurses’ competencies are examples of expertise needed for well-designed clinical trials, nurses may have limited experience in providing insights.

Methods:

Resource development included a literature review and usability testing by multiple stakeholders.

Results:

Usability testing indicated the resource was comprehensive and relevant to pharmaceutical and nonpharmaceutical studies. Reviewers commented resource prompts are beneficial in assessing study feasibility.

Conclusion:

Sponsors of research need nurse engagement to improve feasibility and flexibility and prevent protocol deviations in clinical trials. Leveraging the “Resource to Support Neonatal Nurse Engagement in Clinical Research©” can enhance research education and foster engagement of nurses in neonatal research.

Implications for Practice:

The resource has implications for the nursing profession, the pharmaceutical industry, and the advancement of new therapies. Individual nurses benefit from education and a framework for research engagement. The profession benefits from enhanced visibility through research collaboration. The pharmaceutical industry gains valuable insights on neonatal care, family dynamics, and NICU standard of care. A resource to foster collaboration in the study development process is an important step for advancing new therapies for neonates.
Paroxysmal Cold Hemoglobinuria: Mild to Catastrophic—Spectrum of a Rare Hemolytic Anemia of Childhood
Authors: Agarwala Sneha , Kalra Manas , Sachdeva Anupam , Anand Kanav , Setia Rasika
Published: September 2024

Paroxysmal cold hemoglobinuria (PCH) is among the rarest forms of autoimmune hemolytic anemia, most often seen in young children. PCH is caused by a biphasic immunoglobulin G antibody that binds to red cells at low temperatures and causes complement-mediated lysis as the temperature is raised. Diagnosis is based on high clinical suspicion followed by confirmation of the presence of Donath-Landsteiner antibodies. We have described 3 cases diagnosed with PCH over a span of 1 year, 2 cases presented with acute kidney injury with variable severity and needed hemodialysis. Another case showed prompt recovery with supportive treatment, suggesting variable severity of PCH. This report intends to generate awareness of this rare condition which is often misdiagnosed as nonspecific autoimmune hemolytic anemia and leads to unnecessary prolonged immunosuppressive therapy. It also emphasizes the rare possibility of the need for prompt renal replacement therapy in an otherwise benign self-limiting disorder.
Progress to Implement the National Strategy on Hunger, Nutrition, and Health at the US Department of Health and Human Services
Authors: Fisher Rachel , Piercy Katrina
Published: September 2024

In 2022, the Biden-Harris Administration held the White House Conference on Hunger, Nutrition, and Health that galvanized public and private sector contributions to help the Administration reach its goals of ending hunger and improving healthy eating and physical activity to reduce diet-related chronic diseases and disparities by 2030. The White House also released a National Strategy on Hunger, Nutrition, and Heath (National Strategy) that listed specific actions for the federal government across 5 pillars, including more than 60 actions for the US Department of Health and Human Services (HHS). This article highlights HHS achievements over the 2 years since the National Strategy was released and identifies opportunities for further collaboration with the private sector to expand efforts to end hunger, improve healthy eating and physical activity, and reduce rates of chronic disease.
Contraceptive Care in the Rheumatic Diseases
Authors: Luche Nicole , Talabi Mehret Birru
Published: September 2024

Contraception can help individuals with rheumatic and musculoskeletal diseases (RMDs) to avoid undesired pregnancies and improve reproductive outcomes. Despite the importance of contraception in the care of females with RMDs, evidence suggests that many of these individuals do not receive consistent or disease-specific counseling regarding contraceptive options. This includes female patients receiving teratogenic prescriptions as part of the management of their RMDs, or who have severe disease activity that might culminate in adverse pregnancy and perinatal outcomes. Contraceptive counseling can help females with RMDs who wish to prevent pregnancy to select a contraceptive method that is best for them.

We conducted a narrative review of the primary literature addressing reversible, prescription-based contraception for females with RMDs, framed by published guidelines on contraceptive safety. Many safe and effective contraceptive options are available for females with RMDs. Special considerations must be given to individuals with systemic lupus erythematosus, whose disease activity may be exacerbated by exogenous estrogen. Females with positive antiphospholipid antibodies should avoid estrogen-containing contraception due to an unacceptable risk of thrombosis and should conditionally avoid depot medroxyprogesterone acetate, which appears to have a prothrombotic signature. Limited contraceptive options are available to male patients. Contraceptive care for adolescents with RMDs can be extrapolated from guidelines written for adult patients, with the additional consideration of barrier protection for individuals at risk for sexually transmitted infections. Future research is needed to assess the effects of contraception use on rheumatic disease activity and side effects.
Reproductive Health in RA, Lupus, and APS
Authors: Zucchi Dina , Tani Chiara , Mosca Marta
Published: September 2024

Systemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis are chronic autoimmune diseases affecting women of childbearing age. These diseases may impair fertility and fecundity, as well as complicate pregnancy and the puerperium in these patients including disease flare and obstetric complications on both the maternal and fetal side. For each patient, an appropriate preconceptional counseling with risk stratification is required, including assessment of disease activity, organ involvement, serological profile, and comorbidities.

In cases of pregnancy, the aims of treatment are to prevent disease activity, to treat disease activity in cases of flare, and to prevent maternal and fetal complications such as preeclampsia or fetal loss. In all patients with these diseases, close clinical monitoring during pregnancy and puerperium is mandatory. This review aims to summarize the fertility issues in patients with systemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis and to provide an update on pregnancy management and outcomes in these patients.
Hepatic Inflammatory Pseudotumor on 18F-FDG and 18F-FAP-42 PET/CT
Authors: Luo Yingqi , Qin Xiaowen , Liu Ying
Published: September 2024

Hepatic inflammatory pseudotumor is a rare benign disease. We describe the 18F-FDG and 18F-FAPI-42 PET/CT findings of hepatic inflammatory pseudotumor in a 57-year-old man. Compared with 18F-FDG, 18F-FAPI-42 PET/CT identified more lesions and showed more intense uptake within the lesions. This case illustrates that hepatic inflammatory pseudotumor should be contemplated in the differential diagnosis of liver lesions with increased 18F-FDG and 18F-FAPI-42 uptake. 18F-FAPI-42 PET/CT might be used as a helpful tool for evaluating hepatic inflammatory pseudotumor.
Evaluation of Attitudes and Perceptions in Students About the Use of Artificial Intelligence in Craniomaxillofacial Surgery
Authors: Guler Ridvan , Yalcin Emine , Gulsun Belgin
Published: September 2024

Developments in technology have created great changes in the field of medicine and dentistry. Artificial intelligence technology is one of the most important innovations that caused this change. This study aimed to evaluate the opinions of dentistry students regarding the use of artificial intelligence in dentistry and craniomaxillofacial surgery. Two hundred ninety-six dentistry students between the ages of 19 and 30 participated in the study. Participants submitted the survey by e-mail examining the student's opinions and attitudes regarding the use of artificial intelligence in dentistry and craniomaxillofacial surgery. Respondents' anonymity was ensured. 47.30% (n: 140) of the students participating in the study are fourth-year students, and 52.70% (n: 156) are fifth-year students. While 48.98% (n: 145) of the participants have knowledge about the uses of artificial intelligence in daily life, 28.37% (n: 84) of the students have knowledge about robotic surgery. While ~74% of the participants think that artificial intelligence will improve the field of dentistry and craniomaxillofacial surgery, it has been observed that they are not worried about these applications replacing dentists in the future. It was determined that there was no statistically significant difference between fourth-year and fifth-year students in their knowledge levels about the areas of use of artificial intelligence (P=0.548). Students’ opinions show that 74% agree that artificial intelligence will lead to major advances in the field of dentistry and craniomaxillofacial surgery. This shows the relationship between dentists and artificial intelligence points to a bright future.
Quantification of Changes in Chin Morphometric Parameters Following Feminization Genioplasty
Authors: Hu Kevin Gao , Parikh Neil , Ihnat Jacqueline , Flores-Pérez Paula , Williams Mica , Almeida Mariana , Allam Omar , Alperovich Michael
Published: September 2024

Genioplasty is frequently performed in facial feminization surgery, typically aiming to reduce chin height and projection for more feminine appearance. Quantification of the bony changes occurring during surgery have to date not been published. This study presents a method for segmentation of the chin using CT imaging to quantify changes to the chin after feminization genioplasty. CT scans of 21 patients before and after feminization genioplasty were segmented in Mimics to isolate the chin region. Surface area, volume, vertical chin projection, and horizontal chin projection were measured before and after surgery. Patient outcomes were evaluated using the FACE-Q and World Health Organization Quality of Life patient-reported outcome measures. Surface area, volume, and vertical chin projection demonstrated statistically significant decreases after surgery. The magnitude of changes in surface area and vertical chin projection were significantly associated with their presurgical values. In particular, patients with greater presurgical vertical projections experienced greater decreases in vertical projection after surgery, with some patients having increases in postsurgical vertical projection. Patient FACE-Q scores improved significantly on all scales, including chin, jawline, and neck satisfaction. This study demonstrates a method for evaluating bony changes on CT scan after feminization genioplasty. The measured changes cohere with the changes expected to create a more feminine chin. Furthermore, changes created by feminization genioplasty are in the context of the patient’s overall facial harmony and are not uniform across all patients.
Triple Pedicled Flap Reconstruction for the Pharyngeal Necrosis: One-stage Suture of the Deltoid-pectoral Flap Harvesting Area
Authors: Onoda Satoshi , Katsuragi Ryohei , Kobayashi Kohta , Satake Toshihiko
Published: September 2024

The patient was a 71-year-old male with hypopharyngeal carcinoma who underwent right-sided neck dissection for lymph node metastasis, adjuvant radiotherapy (70 Gy), and cisplatin chemotherapy, he developed neck inflammation with evidence of free air on computed tomography and subcutaneous fistula formation on laryngoscopy. After total laryngectomy, bilateral neck vessels were obscured by scar tissue secondary to radiotherapy and chronic inflammation. Pedicled pectoralis major (PM) flap was favored for reconstruction. A 20×7 cm PM flap was harvested from the right thoracic region, and the muscle body was harvested caudally to obliterate the dead space in the neck. After complete circumferential suturing, the dead space in the cervical region was filled by suturing the PM muscle body to the exposed cervical spine. A deltoid-pectoral (DP) flap was harvested from the right side and used to create the cephalic aspect of the permanent tracheostoma. In addition, a large right anterior pectoral flap was created lateral to the PM muscle, meticulously preserving the perforating intercostal artery branch during flap elevation. Lastly, the DP flap harvest site and neck defect were temporary. This case report presents a novel technique for laryngeal necrosis reconstruction using a combination of PM, DP, and anterior thoracic flaps. The approach achieved total suture closure of the DP flap harvest site, offering significant advantages. This technique should be considered in patients undergoing reconstruction with DP flaps.
Making Living-donor Liver Transplantation a Viable Option for Patients With Portopulmonary Hypertension
Authors: Burton Kristen , Gold Andrew , Abt Peter , Machado Nolan , Rock Kristen , Bezinover Dmitri
Published: September 2024

Liver transplantation (LT) in patients with significant portopulmonary hypertension (PoPH) is associated with an increased risk of several complications, including graft failure. Graft loss is one of the major reasons. Living donor LT (LDLT) is not routinely performed in the United States in this patient population. In addition, ethical considerations often preclude donation from healthy donors in the setting of a procedure associated with an elevated risk of recipient morbidity and mortality. However, LDLT allows LT to be performed electively, using a superior graft with an improved probability of a good outcome. The key to success in managing these patients is establishing a multidisciplinary team that follows an institutional protocol with clear evaluation and management criteria. These criteria include screening and early diagnosis as well as treatment of PoPH with the goal of optimizing pulmonary arterial hemodynamics and maintaining right ventricular function. Any protocol should include admitting the patient to the hospital a day before surgery for placement of a pulmonary artery catheter to measure and derive relevant hemodynamic variables. A multidisciplinary team should determine the fitness for a transplant a after a careful review of the most up-to-date clinical information. Finally, the team prescribes and executes a plan for optimization and safe perioperative management of the patient. In this report, we discuss our approach to the perioperative management of a patient with significant PoPH who safely underwent LDLT with an excellent postoperative outcome.
Cryptococcus albidus (Naganishia albida) meningitis in a young Patient with T-cell Acute Lymphoblastic Leukemia
Authors: Prasad Amber , Singh Minakshi , Anand Priyal
Published: September 2024

Cryptococcus albidus, an emerging pathogen, poses diagnostic and therapeutic challenges, especially in immunocompromised patients. We report a C. albidus meningitis case in a young T cell-ALL patient, initially suspected of HSV encephalitis. CSF analysis confirmed C. albidus, leading to antifungal therapy with liposomal amphotericin B and flucytosine, resulting in clinical improvement. Elevated procalcitonin levels suggest a potential role in fungal infections. This case underscores the importance of early identification and appropriate treatment in C. albidus meningitis.
Improving Retention and HIV Viral Suppression: A Cluster Randomised Pilot Trial of a Lay Counsellor Motivational Interviewing Training in South Africa
Authors: Onoya Dorina , Sineke Tembeka , Mokhele Idah , Vujovic Marnie , Holland Kate , Ruiter Robert A.C.
Published: September 2024

We piloted a Motivational Interviewing (MI) training program for lay counsellors in South Africa (SA) to assess its impact on retention and viral suppression among newly diagnosed individuals living with HIV (PLHIV) at 12 months post-diagnosis. We randomized eight primary healthcare clinics (PHC) in Johannesburg to either the intervention clinics (n=4) where all lay counsellors were supported for 12 months before the PLHIV enrolment or the standard of care (n=4 clinics). Overall, 548 adults (≥ 18 years) PLHIV were recruited after HIV diagnosis from March 2020 to August 2021 (n=291 intervention, n=257 control). We conducted Poisson regression modelling to assess the intervention effect on patient attendance status (out of care – being ≥28 days late for the last appointment) and viral suppression (<50 copies/ml) at 12 months, reporting risk ratios (RR) with 95% confidence intervals (CIs). Of the 548 eligible participants enrolled, 56.3% were ≥28 days late (52.9% intervention vs 60.9% controls, RR 0.9, 95% CI: 0.7-1.0). Retention at 12 months positively correlated with baseline counselor MI skill levels (Cultivating change talk, RR 1.6, 95%CI: 1.1-2.5; Softening sustain talk, RR 1.5, 95%CI: 0.8-2.9; Empathy, RR 1.4, 95%CI: 1.0-1.8; Partnership RR 1.5, 95%CI: 1.2-1.9). Among those retained at 12 months, 65.3% of intervention participants were virally suppressed compared to 49.3% controls (RR 1.3, 95%CI: 1.0-1.7). Compared to control participants, the intervention group reported more positive counseling experiences, fewer concerns about HIV disclosure (RR 0.8 for high vs low-medium concerns, 95% CI: 0.7–1.0) and ART (RR 0.8, 95% CI: 0.7–1.0), and were more likely to express high confidence to take treatment in public (47.4% vs 28.8%, RR 1.4, 95% CI: 1.0–1.8) after counselling.
Investigating the oxidative stress-vascular brain injury axis in mild cognitive impairment of the Alzheimer type
Authors: Detcheverry Flavie E. , Senthil Sneha , Motue Winnie L.K. , Hosein Chris , Arnaoutelis Rozie , Araujo David , Fetco Dumitru , Assemlal Haz-Edine , Antel Samson , Arnold Douglas L. , Near Jamie , Schipper Hyman M. , Badhwar AmanPreet , Narayanan Sridar
Published: September 2024

INTRODUCTION

Oxidative stress may contribute to brain injury in Alzheimer disease (AD) continuum. The antioxidant glutathione (GSH) can be assessed with magnetic resonance spectroscopy (MRS). Since the relationship between GSH and vascular-brain injury is unknown in the AD continuum, we address this gap in mild cognitive impairment (MCI).

METHODS

3T MRI/MRS data were obtained from 31 MCI participants. GSH and total N-acetylaspartate (tNAA; neuroaxonal integrity marker) were measured in posterior cingulate cortex (PCC) and frontal white matter (FWM). Cerebrovascular injury was assessed using white matter hyperintensity (WMH) volume. Global and regional brain tissue integrity were assessed using normalized brain (NBV) and hippocampal volumes.

RESULTS

Significant associations were reported in FWM between GSH/total creatine (tCr) and tNAA/tCr, and between GSH and both WMH and NBV. tNAA, GSH/tCr, and tNAA/tCr were higher in PCC than FWM.

DISCUSSION

Our results suggest that oxidative stress contributes to vascular-brain injury in MCI.
Caesarean myomectomy is not a risk factor for blood products transfusion among pregnant individuals with fibroids: a retrospective cohort study
Authors: Jarvi S , Aviram A , Joliffe C , Wortsman S , Liu GY , Berndl A , Barrett J , Kroft J
Published: September 2024

Background

Uterine fibroids are common benign tumors during reproductive age. Among pregnant individuals with uterine fibroids, myomectomy at the time of cesarean delivery (CD) allows individuals to avoid a second surgery later in life.

Objective

To examine the safety of myomectomy performed at the time of CD and the factors that increase the risk of greater blood loss in cesarean myomectomy.

Study design

This was a retrospective cohort study of all cesarean myomectomies (CM) performed at a tertiary care center in Toronto, Ontario between January 1, 2012, and June 1, 2019. The study group included individuals who had CM, and the control group included individuals with fibroids who had a CD without removing their fibroids. The primary outcome was the rate of blood products transfusion. Secondary outcomes were the need for hysterectomy and estimated blood loss (EBL). Subgroup analyses were performed for fibroid size, previous CD, and elective vs urgent CD. Logistic regression analysis was performed to assess for confounders.

Results

Overall, 110 CM were compared with 152 CD. The overall transfusion rate for CM was 7.3% compared to 0.7% in the control group (p = 0.005). All procedures requiring transfusion from both groups were performed < 370/7weeks of gestation. In logistic regression analysis, performing a myomectomy was not associated with a higher risk for transfusion. The only factors associated with transfusion were preterm birth (aOR 14.43, p=0.049) and low pre-operative hemoglobin (aOR 0.90, p=0.02). The median reported EBL was 800 mL for CM and 700 mL for controls (p<0.001). No individuals in either group required concomitant hysterectomy. Subgroup analysis showed that fibroid size ≥5cm and previous CD were not associated with increased risk of transfusion among those who had a CM, while urgent CM was significantly associated with the need for transfusion (p=0.02).

Conclusion

This study demonstrates that the transfusion rate was not significantly higher in those undergoing CM at term, compared to those with fibroids undergoing CD without a myomectomy.
VAREANT: a bioinformatics application for gene variant reduction and annotation
Authors: Narayanan Rishabh , DeGroat William , Peker Elizabeth , Ahmed Zeeshan
Published: September 2024

The analysis of high-quality genomic variant data may offer a more complete understanding of the human genome, enabling researchers to identify novel biomarkers, stratify patients based on disease risk factors, and decipher underlying biological pathways. Although the availability of genomic data has sharply increased in recent years, the accessibility of bioinformatic tools to aid in its preparation is still lacking. Limitations with processing genomic data primarily include its large volume, associated computational and storage costs, and difficulty in identifying targeted and relevant information. Here, we presentVAREANT, an accessible and configurable bioinformatic tool to support the preparation of variant data into a usable analysis-ready format. Designed to simplify the data pre-processing workflow,VAREANTenables the curation of targeted variant datasets.VAREANTis comprised of three standalone modules: (1) Pre- processing, (2) Variant Annotation, (3) Artificial Intelligence (AI) / Machine Learning (ML) Data Preparation. Pre-processing supports the fine-grained filtering of complex variant datasets to eliminate extraneous data. Variant Annotation allows for the addition of variant metadata from public annotation databases for subsequent analysis and interpretation. AI/ML Data Preparation supports the user in creating AI/ML-ready datasets suitable for immediate analysis with minimal pre-processing required. We have successfully tested and validated our tool on numerous variable-sized datasets and implementedVAREANTin two case studies involving patients with CVDs. Efficiently extracting relevant variants into an AI/ML ready format using tools likeVAREANThas important scientific implications, such as producing targeted and high-quality datasets and helping reduce overall computational costs.
Acute Kidney Injury and Perioperative complications based on modality of nephrectomy for the treatment of kidney cancer
Authors: Patel Maulinkumar N. , Shah Deep , Patel Heli , Jaimes Edgar A.
Published: September 2024

Background

Nephrectomy, either partial or radical, is a key treatment for kidney cancer. The surgical approach—open, laparoscopic, or robot-assisted—can influence perioperative outcomes. This study evaluates acute kidney injury (AKI) and perioperative complications across these modalities.

Methods

We conducted a retrospective analysis using the National Inpatient Sample (NIS) of 2020–2021 to examine 12,676 kidney cancer patients who underwent nephrectomy. Patients were stratified by surgical approach: open, laparoscopic, and robot-assisted. Primary outcomes included AKI incidence, length of stay, and intra- and post-operative complications. Multivariable regression models adjusted for confounding variables, including age, sex, race, Charlson Comorbidity Index (CCI), hospital region, and teaching status.

Results

Patients undergoing open nephrectomy had the highest AKI rates, particularly for radical nephrectomy (22.13% vs. 16.52% for robotic, p < 0.001). Similarly, patients treated with open surgery had longer hospital stays and higher rates of complications, including pulmonary (7.71% vs. 4.17%, p < 0.001) and vascular (12.11% vs. 4.01%, p < 0.001) in radical nephrectomy. Multivariate analysis confirmed the increased risk of AKI and complications in open nephrectomy, with robotic-assisted surgery demonstrating the best perioperative outcomes.

Conclusion

Open nephrectomy, whether partial or radical, is associated with higher AKI rates and perioperative complications compared to laparoscopic and robot-assisted surgeries. Robot-assisted nephrectomy, with its lower complication rates and shorter hospital stays, may be the preferred approach when feasible. Further efforts to expand access to minimally invasive techniques could improve outcomes for kidney cancer patients.
Erythropoietin single nucleotide polymorphisms are associated with anemia and dyslipidemia in a cardiovascular disease population
Authors: Northrup Victoria , Eadie Ashley L. , Nelson Victoria L. , D’Souza Kenneth , Hassan Ansar , Pulinilkunnil Thomas , Kienesberger Petra , Légaré Jean-Francois , Simpson Jeremy A. , Brunt Keith R.
Published: September 2024

Human erythropoietin (EPO) is an essential erythropoietic cytokine and recombinant biological therapeutic in anemia in chronic kidney disease. Single nucleotide polymorphisms (SNPs) in EPO have been linked to anemia and diabetic microvascular complications but no other cardiovascular comorbidities like dyslipidemia or hypertension. Here identified a clinical cohort of cardiovascular patients with anemia, dyslipidemia, hypertension, type-2 diabetes, or heart failure with preserved ejection fraction. Sanger sequencing was used for genotyping three EPO SNPs (rs1617640, rs507392 and rs551238), which were compared to clinical outcomes with SNPstat and clinical parameters profiles by student t-test. Nonstandard clinical chemistry measures of plasma EPO, hepcidin, transferrin, and ferritin were determined by ELISA. In the additive model, the C allele of rs1617640 was associated with lower EPO and anemia. In the recessive model, the SNP rs507392 genotype of GG was associated with dyslipidemia, which was associated with lower EPO in plasma and elevated total cholesterol and low-density lipoproteins. Interestingly, the G allele of rs507392 was found to be associated with hypertension, but only in females. Here we show that the SNPs in EPO are a potential risk factor for anemia, dyslipidemia, and hypertension in cardiovascular disease patients.
Depression Incidence in Patients with Hypertension in a Single Outpatient Center
Authors: Amoateng Richard , Arunthamakun Natthew , Tierliwaerdi Xiarepati , Johnston Alexandra , Gadani Mrudula
Published: September 2024

Introduction

Hypertension and depression are both highly prevalent in the United States and each condition is commonly managed in the outpatient setting. This study aims to investigate the incidence of depression in patients who are diagnosed with hypertension.

Methods

A retrospective cohort study was conducted analyzing 9,240 adult patients at a single center outpatient clinic between 2019 and 2022. Blood pressure and PHQ-9 from the latest outpatient visit were recorded. Demographic data associated with hypertension were also obtained. Bivariate statistical analysis was performed. Multivariate linear and logistic regression models were adjusted for co-morbid conditions.

Results

Out of the 9,240 patients studied, 3,694 (40%) had a diagnosis of hypertension. Patients with hypertension were more likely to be older (61.96 ± 14.95 vs 39.85 ± 15.61, p=0.000), male (37% vs 33%, p =0.002) and black (45.2% vs 23.3%, p<0.001) compared with those without a diagnosis of hypertension. The mean PHQ-9 score was higher in patients with hypertension than in those without (2.97 ±4.66 vs 2.70 ± 4.93, p=0.000). Patients with hypertension were more likely to have uncontrolled depression defined as PHQ-9 score >4 (22.55% vs 19.4%, p<0.001) even when adjusted for co-morbid conditions (adj OR 1.216 95% CI 1.06 -1.34 p=0.005).

Conclusions

In this cohort of patients, a diagnosis of hypertension was associated with an increased rate of uncontrolled depressive symptoms. Hence patients with hypertension should be screened using validated PHQ-9 tools in the outpatient setting and offered appropriate treatment for depression.
Emergency admission plasma D-dimer and Prothrombin activity in acute ischemic stroke with large artery occlusion
Authors: Jiang Shandong , Guo Peizheng , Qian Cong , Yu Jun , Xu Liang , Li Xu , Chen Xianyi , Bing Fang , Yuan Yuan , Tan Zhongju , Xu Jing , Li Jianru
Published: September 2024

Background

The coagulation system is intrinsically linked to pathological mechanism and progression of ischemic stroke. However, the role of preoperative coagulation function in determining the functional outcomes of acute ischemic stroke patients following large artery occlusion (AIS-LVO) has not been extensively evaluated in peer-reviewed literature.

Methods

We utilized logistic regression analyses, complemented by the construction of receiver operating characteristic (ROC) curves, to identify significant predictive factors for poor prognosis following EVT. Additionally, subgroup analyses were conducted to further assess the prognostic efficacy of coagulation function across different subgroups.

Results

A total of 607 patients were enrolled, with 335 (55.19%) experiencing an unfavorable outcome. Multivariate regression analysis identified preoperative D-dimer and PTA as independent predictors of 3-month prognosis. After adjusting for confounders, elevated preoperative D-dimer levels (≥715 mg/L), identified by cut-off value, were a significant predictor of poor prognosis, with 2.51-fold higher risk compared to the normal range. Conversely, elevated PTA levels (≥85.5%) were significantly and inversely associated with poor prognosis, indicating a reduced risk of 0.39 times. Furthermore, the combination of elevated D-dimer and reduced PTA demonstrated a synergistic effect, markedly increasing the risk of poor outcomes in AIS-LVO patients. Subgroup analyses revealed that failed recanalization, comorbid diabetes, and non-middle cerebral artery (MCA) occlusion significantly influence the predictive value of D-dimer and PTA for clinical outcomes.

Conclusion

Elevated admission D-dimer and reduced PTA levels are an independent predictor of poor prognosis in patients with AIS-LVO, and there is a synergistic interaction between the two variables.
Naturally acquired IgG responses toPlasmodium falciparumdo not target the conserved termini of the malaria vaccine candidate merozoite surface protein 2
Authors: Zerebinski Julia , Margerie Lucille , Han Nan Sophia , Moll Maximilian , Ritvos Matias , Jahnmatz Peter , Ahlborg Niklas , Ngasala Billy , Rooth Ingegärd , Sjöberg Ronald , Sundling Christopher , Yman Victor , Färnert Anna , Plaza David
Published: September 2024

Malaria remains a significant burden, and a fully protective vaccine againstPlasmodium falciparumis critical for reducing morbidity and mortality. Antibody responses against the blood-stage antigen merozoite surface protein 2 (MSP2) are associated with protection fromP. falciparummalaria, but its extensive polymorphism is a barrier to its development as a vaccine candidate. New tools, such as long-read sequencing and accurate protein structure modelling allow us to more easily study the genetic diversity and immune responses towards antigens from clinical isolates. This study sought to better understand naturally acquired MSP2-specific antibody responses. IgG responses against recombinantly expressed full- length, central polymorphic regions, and peptides derived from the conserved termini of MSP2 variants sequenced from patient isolates, were tested in plasma from travelers with recent, acute malaria and from individuals living in an endemic area of Tanzania. IgG responses towards full MSP2 and truncated MSP2 antigens were variant specific. IgG antibodies in the plasma of first-time infected or previously exposed travelers did not recognize the conserved termini of expressed MSP2 variants by ELISA, but they bound 13- amino acid long linear epitopes from the termini in a custom-made peptide array. Alphafold3 modelling suggests extensive structural heterogeneity in the conserved termini upon antigen oligomerization. IgG from individuals living in an endemic region, many who were asymptomatically infected, did not recognize the conserved termini by ELISA. Our results suggest that responses to the variable regions are important for the development of naturally acquired immunity towards MSP2.
Calcium dynamics of skin-resident macrophages during homeostasis and tissue injury
Authors: Guerrero Pearl A. Leon , Rasmussen Jeffrey P. , Peterman Eric
Published: September 2024

Immune cells depend on rapid changes in intracellular calcium activity to modulate cell function. Skin contains diverse immune cell types and is critically dependent on calcium signaling for homeostasis and repair, yet the dynamics and functions of calcium in skin immune cells remain poorly understood. Here, we characterize calcium activity in Langerhans cells, skin-resident macrophages responsible for surveillance and clearance of cellular debris after tissue damage. Langerhans cells reside in the epidermis and extend dynamic dendrites in close proximity to adjacent keratinocytes and somatosensory peripheral axons. We find that homeostatic Langerhans cells exhibit spontaneous and transient changes in calcium activity, with calcium flux occurring primarily in the cell body and rarely in the dendrites. Triggering somatosensory axon degeneration increases the frequency of calcium activity in Langerhans cell dendrites. By contrast, we show that Langerhans cells exhibit a sustained increase in intracellular calcium following engulfment of damaged keratinocytes. Altering intracellular calcium activity leads to a decrease in engulfment efficiency of keratinocyte debris. Our findings demonstrate that Langerhans cells exhibit context-specific changes in calcium activity and highlight the utility of skin as an accessible model for imaging calcium dynamics in tissue-resident macrophages.

SIGNIFICANCE STATEMENT

Calcium activity in immune cells is thought to regulate cell function, but studies focusing on tissue-resident macrophages are limited.

Skin-resident macrophages known as Langerhans cells exhibit rapid and transient changes in calcium activity in homeostatic conditions, which can change depending on the type of tissue injury inflicted. Pharmacological perturbation of calcium activity leads to a decrease in Langerhans cell engulfment.

These findings suggest calcium activity is important for tissue surveillance by Langerhans cells.
Expansionin situgenome sequencing links nuclear abnormalities to hotspots of aberrant euchromatin repression
Authors: Labade Ajay S. , Chiang Zachary D. , Comenho Caroline , Reginato Paul L. , Payne Andrew C. , Earl Andrew S. , Shrestha Rojesh , Duarte Fabiana M. , Habibi Ehsan , Zhang Ruochi , Church George M. , Boyden Edward S. , Chen Fei , Buenrostro Jason D.
Published: September 2024

Microscopy and genomics are both used to characterize cell function, but approaches to connect the two types of information are lacking, particularly at subnuclear resolution. While emerging multiplexed imaging methods can simultaneously localize genomic regions and nuclear proteins, their ability to accurately measure DNA-protein interactions is constrained by the diffraction limit of optical microscopy. Here, we describe expansion in situ genome sequencing (ExIGS), a technology that enables sequencing of genomic DNA and superresolution localization of nuclear proteins in single cells. We applied ExIGS to fibroblast cells derived from an individual with Hutchinson-Gilford progeria syndrome to characterize how variation in nuclear morphology affects spatial chromatin organization. Using this data, we discovered that lamin abnormalities are linked to hotspots of aberrant euchromatin repression that may erode cell identity. Further, we show that lamin abnormalities heterogeneously increase the repressive environment of the nucleus in tissues and aged cells. These results demonstrate that ExIGS may serve as a generalizable platform for connecting nuclear abnormalities to changes in gene regulation across disease contexts.
Integration of light quality signals regulates ABA abundance and stomatal movements during seedling establishment
Authors: Gustavsson Mathilda , Hill Lionel , Franklin Keara A. , Pridgeon Ashley J.
Published: September 2024

Obtaining sufficient light for photosynthesis and avoiding desiccation are two key challenges faced by seedlings during early establishment. Perception of light quality via specialised photoreceptors signals the availability of sunlight for photosynthesis. Canopy shade is depleted in red (R) and enriched in far-red (FR) light, lowering R:FR ratio, while direct sunlight and sunflecks contain UV-B. The balance of these wavelengths can determine the developmental strategy adopted by seedlings to either avoid shade, via stem elongation, or promote the expansion of photosynthetic organs. How seedlings regulate stomatal movements in different light environments is poorly understood. Using FR and UV-B supplementation to mimic aspects of canopy shade and sunlight respectively, we monitored stomatal apertures inArabidopsis thalianacotyledons. We show that low R:FR inhibits stomatal opening via a mechanism involving PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and increased abscisic acid (ABA). In contrast, UV-B perceived by the UV RESISTANCE LOCUS 8 (UVR8) photoreceptor antagonises this response to promote stomatal opening in a response requiring phototropin photoreceptors. The convergence of phytochrome and UVR8 signalling to control ABA abundance enables plants to coordinate stem elongation and water use during seedling establishment in dynamic light environments.
scEMB: Learning context representation of genes based on large-scale single-cell transcriptomics
Authors: Hsieh Kang-Lin , Chu Yan , Li Xiaoyang , Pilié Patrick G. , Dai Yulin
Published: September 2024

Background

The rapid advancement of single-cell transcriptomic technologies has led to the curation of millions of cellular profiles, providing unprecedented insights into cellular heterogeneity across various tissues and developmental stages. This growing wealth of data presents an opportunity to uncover complex gene-gene relationships, yet also poses significant computational challenges.

Results

We present scEMB, a transformer-based deep learning model developed to capture context-aware gene embeddings from large-scale single-cell transcriptomics data. Trained on over 30 million single-cell transcriptomes, scEMB utilizes an innovative binning strategy that integrates data across multiple platforms, effectively preserving both gene expression hierarchies and cell-type specificity. In downstream tasks such as batch integration, clustering, and cell type annotation, scEMB demonstrates superior performance compared to existing models like scGPT and Geneformer. Notably, scEMB excelsin silicocorrelation analysis, accurately predicting gene perturbation effects in CRISPR-edited datasets and microglia state transition, identifying a few known Alzheimer’s disease (AD) risks genes in top gene list. Additionally, scEMB offers robust fine-tuning capabilities for domain-specific applications, making it a versatile tool for tackling diverse biological problems such as therapeutic target discovery and disease modeling.

Conclusions

scEMB represents a powerful tool for extracting biologically meaningful insights from complex gene expression data. Its ability to modelin silicoperturbation effects and conduct correlation analyses in the embedding space highlights its potential to accelerate discoveries in precision medicine and therapeutic development.