bluuebunny/crossref_metadata_2025 huggingface dataset:
Respiratory event index underestimates severity of sleep apnea compared to apnea-hypopnea index
Authors: Pitkänen Minna , Nath Rajdeep Kumar , Korkalainen Henri , Nikkonen Sami , Mahamid Alaa , Oksenberg Arie , Duce Brett , Töyräs Juha , Kainulainen Samu , Leppänen Timo
Published: December 2023

Polygraphy (PG) is often used to diagnose obstructive sleep apnea (OSA). However, it does not use electroencephalography, and therefore cannot estimate sleep time or score arousals and related hypopneas. Consequently, the PG-derived respiratory event index (REI) differs from the polysomnography (PSG)-derived apnea-hypopnea index (AHI). In this study, we comprehensively analyzed the differences between AHI and REI. Conventional AHI and REI were calculated based on total sleep time (TST) and total analyzed time (TAT), respectively, from two different PSG datasets (n = 1561). Moreover, TAT-based AHI (AHITAT) and TST-based REI (REITST) were calculated. These indices were compared keeping AHI as the gold standard. The REI, AHITAT, and REITST were significantly lower than AHI (p < 0.0001, p ≤ 0.002, and p ≤ 0.01, respectively). The total classification accuracy of OSA severity based on REI was 42.1% and 72.8% for two datasets. Based on AHITAT, the accuracies were 68.4% and 85.9%, and based on REITST, they were 65.9% and 88.5% compared to AHI. AHI was most correlated with REITST (r = 0.98 and r = 0.99 for the datasets) and least with REI (r = 0.92 and r = 0.97). Compared to AHI, REI had the largest mean absolute errors (13.9 and 6.7) and REITST the lowest (5.9 and 1.9). REI had the lowest sensitivities (42.1% and 72.8%) and specificities (80.7% and 90.9%) in both datasets. Based on these present results, REI underestimates AHI. Furthermore, these results indicate that arousal-related hypopneas are an important measure for accurately classifying OSA severity.
Dynamin‐related protein 1 is a critical regulator of mitochondrial calcium homeostasis during myocardial ischemia/reperfusion injury
Authors: Piao Lin , Fang Yong‐Hu , Fisher Michael , Hamanaka Robert B. , Ousta Alaa , Wu Rongxue , Mutlu Gökhan M. , Garcia Alfredo J. , Archer Stephen L. , Sharp Willard W.
Published: December 2023

Dynamin‐related protein 1 (Drp1) is a cytosolic GTPase protein that when activated translocates to the mitochondria, meditating mitochondrial fission and increasing reactive oxygen species (ROS) in cardiomyocytes. Drp1 has shown promise as a therapeutic target for reducing cardiac ischemia/reperfusion (IR) injury; however, the lack of specificity of some small molecule Drp1 inhibitors and the reliance on the use of Drp1 haploinsufficient hearts from older mice have left the role of Drp1 in IR in question. Here, we address these concerns using two approaches, using: (a) short‐term (3 weeks), conditional, cardiomyocyte‐specific, Drp1 knockout (KO) and (b) a novel, highly specific Drp1 GTPase inhibitor, Drpitor1a. Short‐term Drp1 KO mice exhibited preserved exercise capacity and cardiac contractility, and their isolated cardiac mitochondria demonstrated increased mitochondrial complex 1 activity, respiratory coupling, and calcium retention capacity compared to controls. When exposed to IR injury in a Langendorff perfusion system, Drp1 KO hearts had preserved contractility, decreased reactive oxygen species (ROS), enhanced mitochondrial calcium capacity, and increased resistance to mitochondrial permeability transition pore (MPTP) opening. Pharmacological inhibition of Drp1 with Drpitor1a following ischemia, but before reperfusion, was as protective as Drp1 KO for cardiac function and mitochondrial calcium homeostasis. In contrast to the benefits of short‐term Drp1 inhibition, prolonged Drp1 ablation (6 weeks) resulted in cardiomyopathy. Drp1 KO hearts were also associated with decreased ryanodine receptor 2 (RyR2) protein expression and pharmacological inhibition of the RyR2 receptor decreased ROS in post‐IR hearts suggesting that changes in RyR2 may have a role in Drp1 KO mediated cardioprotection. We conclude that Drp1‐mediated increases in myocardial ROS production and impairment of mitochondrial calcium handling are key mechanisms of IR injury. Short‐term inhibition of Drp1 is a promising strategy to limit early myocardial IR injury which is relevant for the therapy of acute myocardial infarction, cardiac arrest, and heart transplantation.
A deep learning–based system to identify originating mural layer of upper gastrointestinal submucosal tumors under EUS
Authors: Li Xun , Zhang Chenxia , Yao Liwen , Zhang Jun , Zhang Kun , Feng Hui , Yu Honggang
Published: December 2023

Background and Objective

EUS is the most accurate procedure to determine the originating mural layer and subsequently select the treatment of submucosal tumors (SMTs). However, it requires superb technical and cognitive skills. In this study, we propose a system named SMT Master to determine the originating mural layer of SMTs under EUS.

Materials and Methods

We developed 3 models: deep convolutional neural network (DCNN) 1 for lesion segmentation, DCNN2 for mural layer segmentation, and DCNN3 for the originating mural layer classification. A total of 2721 EUS images from 201 patients were used to train the 3 models. We validated our model internally and externally using 283 images from 26 patients and 172 images from 26 patients, respectively. We applied 368 images from 30 patients for the man-machine contest and used 30 video clips to test the originating mural layer classification.

Results

In the originating mural layer classification task, DCNN3 achieved a classification accuracy of 84.43% and 80.68% at internal and external validations, respectively. In the video test, the accuracy was 80.00%. DCNN1 achieved Dice coefficients of 0.956 and 0.776 for lesion segmentation at internal and external validations, respectively, whereas DCNN2 achieved Dice coefficients of 0.820 and 0.740 at internal and external validations, respectively. The system achieved 90.00% accuracy in classification, which is comparable with that of EUS experts.

Conclusions

Our proposed system has the potential to solve difficulties in determining the originating mural layer of SMTs in EUS procedures, which relieves the EUS learning pressure of physicians.
Factors affecting the diagnostic value of liquid-based cytology by EUS-FNA in the diagnosis of pancreatic cystic neoplasms
Authors: Du Chen , He Zhengting , Gao Fei , Li Longsong , Han Ke , Feng Xiuxue , Wang Xiangdong , Tang Ping , Chai Ningli , Linghu Enqiang
Published: December 2023

Background and Objectives

This study retrospectively evaluated the value of liquid-based cytology (LBC) alone for diagnosing pancreatic cystic neoplasms (PCNs) in a large sample and initially estimated factors that might affect LBC diagnostic ability.

Methods

From April 2015 to October 2022, we prospectively enrolled 331 patients with suspected PCNs in our prospective database. Among them, 112 patients chosen to receive surgical resection were included. Only 96 patients who underwent EUS-guided cystic fluid LBC were finally studied. The diagnostic values of LBC for differentiating benign and malignant PCNs and subtypes of PCNs were evaluated.

Results

There were 71 female and 25 male patients with a mean age of 47.6 ± 14.4 years. The median cyst size was 43.4 mm. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of LBC for the differentiation of benign and malignant PCNs were 96.9%, 57.1%, 100%, 100%, and 96.7%, respectively. The overall diagnostic accuracy of LBC for specific cyst types was 33.3% (32/96). Cysts located in the pancreatic body/tail or with irregular shapes were more likely to obtain a definite LBC diagnosis. At the same time, age, sex, tumor size, cystic fluid viscosity, operation time, needle type, and presence of septation were not significantly different.

Conclusion

Liquid-based cytology alone is useful for differentiating benign PCNs from malignant PCNs and can successfully characterize the PCN subtypes in one-third of patients. Pancreatic cystic neoplasms located in the body/tail or exhibiting irregular shapes are more likely to obtain a definite LBC diagnosis.
Plastic Surgery: Beware the Candle Burning at Both Ends
Authors: Brown Kathryn W. , Moss Clayton A. , McCandless Martin G. , Mukit Muntazim , Walker Marc E.
Published: December 2023

Background:

Plastic surgery dates back to 800 BC, where forehead flaps were used to reconstruct noses in India. Today, it is one of the most romanticized fields in medicine. Due to the influence of social media, there has never been a larger spotlight. Ironically, this spotlight brings a narrowed perception of the scope of plastic surgery. This study aimed to assess the scope through the eyes of the average American to identify gaps in knowledge to better represent the field.

Methods:

A series of questions were developed under survey methodologists and administered by Qualtrics. Responses were gathered, and data were analyzed to assess the public’s knowledge of plastic surgery’s scope.

Results:

Two thousand five hundred responses were obtained, balanced across demographics similar to that of the United States. The US population has a poor understanding of the scope of plastic surgery and how to obtain board certification.

Conclusions:

This survey demonstrates a gap in awareness of plastic surgery as a field and the scope outside aesthetic procedures dramatized by the media. There remains no clear understanding of the qualifications of plastic surgeons or the provider makeup of the field of cosmetic surgery. Subspecialties proved to be overlooked, and knowledge of board certification was sparse. Further effort is needed to educate both the public and patients of the scope of plastic surgery, so that they might seek and gain access to appropriate treatment in the most efficient manner to optimize outcomes regarding the form and function of the body.
Optimizing the Yield of In-and-Out Urinary Catheter Cultures by Applying a “Midstream-Like” Approach in Pediatric Patients
Authors: Kriger Or , Belausov Natasha , Gefen-Halevi Shiraz , Smollan Gillian , Sanalla Roanda , Merchi Yelena , Levin Asher , Tunkel Gil , Feldman Oren , Amit Sharon
Published: December 2023

Despite appropriate disinfection, sample contamination during in-and-out urinary catheterization is not uncommon, yielding false-positive and “mixed-culture” interpretations. We implemented a “midstream-like” catheterization technique, and cultured both first- and second-voided urine fractions. Second-fraction cultures exhibited less contaminants and “mixed-culture” interpretations and were better aligned with pyuria, thereby enhancing diagnostic accuracy and minimizing the risk of clinical misdiagnosis and unwarranted antibiotic use.
Treatment Delay of Febrile Urinary Tract Infections Among Infants With Respiratory Symptoms
Authors: Iio Kazuki , Mikami Naoaki , Harada Ryoko , Hamada Riku , Hagiwara Yusuke , Hataya Hiroshi , Sandhu Ash , Goldman Ran D.
Published: December 2023

Objective:

To evaluate whether antibiotic treatment of febrile urinary tract infection (UTI) is delayed in febrile infants with respiratory symptoms compared with those without.

Study Design:

Data of infants 2–24 months of age diagnosed with UTI from March 1, 2012 to May 31, 2023 were collected from our hospital’s medical charts and triage records. Patients with known congenital anomalies of the kidney and urinary tract or a history of febrile UTI were excluded. Patients were classified as having respiratory symptoms if they had any of the following symptoms or clinical signs: cough, rhinorrhea, pharyngeal hyperemia and otitis media. Time to first antibiotic treatment from fever onset was compared between patients with and without respiratory symptoms. A Cox regression model was constructed to adjust for potential confounders.

Results:

A total of 214 patients were eligible for analysis. The median age of the eligible patients was 5.0 months (interquartile range: 3.0–8.8) and 118 (55%) were male. There were 104 and 110 patients in the respiratory symptom and no respiratory symptom groups, respectively. The time to first antibiotic treatment was significantly longer in the group with respiratory symptoms (51 hours vs. 21 hours). Respiratory symptoms were significantly associated with a longer time to first treatment after adjustment for age and sex in the Cox regression model (hazard ratio = 0.63, 95% confidence interval: 0.47–0.84).

Conclusions:

Treatment of febrile UTI infants with respiratory symptoms tends to be delayed. Pediatricians should not exclude febrile UTI even in the presence of respiratory symptoms.
Overcoming the challenges of scalable iPSC generation in translation medicine
Authors: Liu Ding-Hao , Tseng Huan-Chin , Lee Meng-Shiue , Chiou Guang-Yuh , Wang Chin-Tien , Lin Yi-Ying , Lai Wei-Yi , Liu Yu-Hao , Wang Chien-Ying , Lee Chen-Yi , Kao Chung-Lan , Chen Cheng-Fong , Chien Yueh
Published: December 2023

Background:

The potential of induced pluripotent stem cells (iPSCs) in revolutionizing regenerative medicine cannot be overstated. iPSCs offer a profound opportunity for therapies involving cell replacement, disease modeling, and cell transplantation. However, the widespread application of iPSC cellular therapy faces hurdles, including the imperative to regulate iPSC differentiation rigorously and the inherent genetic disparities among individuals. To address these challenges, the concept of iPSC super donors emerges, holding exceptional genetic attributes and advantageous traits. These super donors serve as a wellspring of standardized, high-quality cell sources, mitigating inter-individual variations and augmenting the efficacy of therapy.

Methods:

In pursuit of this goal, our study embarked on the establishment of iPSC cell lines specifically sourced from donors possessing the HLA type (A33:03-B58:01-DRB1*03:01). The reprogramming process was meticulously executed, resulting in the successful generation of iPSC lines from these carefully selected donors. Subsequently, an extensive characterization was conducted to comprehensively understand the features and attributes of these iPSC lines.

Results:

The outcomes of our research were highly promising. The reprogramming efforts culminated in the generation of iPSC lines from donors with the specified HLA type. These iPSC lines displayed a range of distinctive characteristics that were thoroughly examined and documented. This successful generation of iPSC lines from super donors possessing advantageous genetic traits represents a significant stride towards the realization of their potential in therapeutic applications.

Conclusion:

In summary, our study marks a crucial milestone in the realm of regenerative medicine. The establishment of iPSC lines from super donors with specific HLA types signifies a paradigm shift in addressing challenges related to iPSC cellular therapy. The standardized and high-quality cell sources derived from these super donors hold immense potential for various therapeutic applications. As we move forward, these findings provide a solid foundation for further research and development, ultimately propelling the field of regenerative medicine toward new horizons of efficacy and accessibility.
The role of intestinal microecology in inflammatory bowel disease and colorectal cancer: A review
Authors: Li Huimin , Wang Kun , Hao Mengdi , Liu Yin , Liang Xiaoqing , Yuan Dajin , Ding Lei
Published: December 2023

Intestinal microecology is a dominant and complex microecological system in human body. Generally, intestinal microecosystem consists of normal symbiotic flora and its living environment (including intestinal epithelial tissue and intestinal mucosal immune system). Commensal flora is the core component of microecology. Both structures of intestinal mucosa and functions of immune system are essential to maintain homeostasis of intestinal microecosystem. Under normal conditions, intestinal microorganisms and intestinal mucosa coordinate with each other to promote host immunity. When certain factors in the intestine are altered, such as disruption of the intestinal barrier causing dysbiosis of the intestinal flora, the immune system of the host intestinal mucosa makes a series of responses, which leads to the development of intestinal inflammation and promotes colorectal cancer. In this review, to further understand the relationship between intestinal microecology and intestinal diseases, we systematically elaborate the composition of the intestinal mucosal immune system, analyze the relationship between intestinal flora and mucosal immune system, and the role of intestinal flora on intestinal inflammatory diseases and colorectal cancer.
Exploration of the effect and mechanism of Scutellaria barbata D. Don in the treatment of ovarian cancer based on network pharmacology and in vitro experimental verification
Authors: Zhang Jie , Qi Cong , Li He , Ding Chenhuan , Wang Libo , Wu Hongjin , Dai Weiwei , Wang Chenglong
Published: December 2023

The mortality rate of ovarian cancer is the highest among gynecological cancers, posing a serious threat to women health and life. Scutellaria barbata D. Don (SBD) can effectively treat ovarian cancer. However, its mechanism of action is unclear. The aim of this study was to elucidate the mechanism of SBD in the treatment of ovarian cancer using network pharmacology, and to verify the experimental results using human ovarian cancer SKOV3 cells. The Herb and Disease Gene databases were searched to identify common targets of SBD and ovarian cancer. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Protein-Protein Interaction (PPI) network analyses were performed to identify the potential molecular mechanisms behind SBD. Finally, the molecular docking and main possible pathways were verified by experimental studies. Cell proliferation, the mRNA expression level of key genes and signaling pathway were all investigated and evaluated in vitro. A total of 29 bioactive ingredients and 137 common targets in SBD were found to inhibit ovarian cancer development. The active ingredients identified include quercetin, luteolin, and wogonin. Analysis of the PPI network showed that AKT1, VEGFA, JUN, TNF, and Caspase-3 shared centrality among all target genes. The results of the KEGG pathway analysis indicated that the cancer pathway, PI3K-Akt signaling pathway, and MAPK signaling pathways mediated the effects of SBD against ovarian cancer progression. Cell experiments showed that quercetin, luteolin, and wogonin inhibited the proliferation and clone formation of SKOV3 cells and regulated mRNA expression of 5 key genes by inhibiting PI3K/Akt signaling pathway. Our results demonstrate that SBD exerted anti-ovarian cancer effects through its key components quercetin, luteolin and wogonin. Mechanistically, its anti-cancer effects were mediated by inhibition of the PI3K/Akt signaling pathways. Therefore, SBD might be a candidate drug for ovarian cancer treatment.
Rare occurrence of pulmonary coinfection involving Aspergillus fumigatus and Nocardia cyriacigeorgica in immunocompetent patients based on NGS: A case report and literature review
Authors: Ye Jiaqing , Li Yahua , Hao Jiahao , Song Minghui , Guo Yumei , Gao Weili , Zheng Cuiying , Huang Yinqi , Feng Zhongjun , Zhang Lijie
Published: December 2023

Rationale:

In our search on PubMed, we found that reports of co-infections involving Aspergillus fumigatus and Nocardia cyriacigeorgica in the literature are notably scarce. Most cases have been documented in patients with compromised immune systems or underlying pulmonary conditions. In contrast, our patient did not present with any of these risk factors. Furthermore, there have been no recent incidents such as near-drowning or other accidents in the patient history. To the best of our knowledge, this case represents a hitherto unreported clinical scenario. To enhance comprehension, we conducted a comprehensive literature review by compiling a total of 20 case reports (spanning from 1984 to 2023) on co-infections involving Aspergillus and Nocardia species, retrieved from PubMed.

Patient concerns and diagnosis:

Chest CT revealed the presence of multiple nodules and clustered high-density shadows in both lungs. Bronchoscopy revealed mucosal congestion and edema in the apical segment of the right upper lobe of the lung, along with the presence of 2 spherical polypoid new organisms. The pathological analysis reported severe chronic inflammation with evidence of Aspergillus within the tissue. Next-Generation Sequencing of bronchoalveolar lavage fluid revealed the presence of reads corresponding to A fumigatus and N cyriacigeorgica. Positive cultures for A fumigatus and the Nocardia genus were yielded by prolonging the incubation of samples in the microbiology laboratory.

Interventions:

Treatment with voriconazole for A fumigatus and sulfamethoxazole-trimethoprim for N cyriacigeorgica infection was given.

Outcomes:

The patient improved and was discharged. After 6 months of telephone follow-up, the patient reported no clinical symptoms, discontinued the medication on his own.

Lessons:

A fumigatus and N cyriacigeorgica can manifest as a co-infection in immunocompetent patients. Clinicians should prioritize the significant advantages and value of NGS in detecting rare and mixed pathogens associated with pulmonary infections.
Patterns and Outcomes of Acute Central Nervous System Complications During Treatment of Childhood Acute Lymphoblastic Leukemia: A Single-center Experience
Authors: Hamoda Asmaa , Bedair Mohamed , Semary Samah Fathy , Youssef Ayda , Hafez Hanafy
Published: December 2023

Central nervous system (CNS) complications are considered adverse events during the treatment of pediatric acute lymphoblastic leukemia (ALL). This study aimed to assess the incidence, types, clinical and radiologic patterns, risk factors, and the fate of different CNS complications during the treatment of pediatric ALL. A retrospective study included 390 patients with pediatric ALL, treated according to St. Jude total XV protocol at the National Cancer Institute, Cairo University, from January 2012 to December 2017. Thirty-nine (10%) patients developed different types of CNS complications. Nineteen (4.9%) patients had cerebrovascular complications, 12 (3.1%) patients had posterior reversible encephalopathy syndrome (PRES), and 6 (1.5%) patients had leukoencephalopathy; both CNS infections and leukemic infiltrates were diagnosed in one patient each. CNS complications were significantly higher in patients older than 10 years old, patients with high-risk disease, and patients who were classified as CNS III status with a statistically significant P value of 0.040, 0.020, and 0.002, respectively. There were 31 (79.5%) cases that achieved complete recovery, 6 (15.4%) patients who died, and 2 (5.1%) patients who developed residual neurological deficits. In conclusion, pediatric patients with ALL, who presented with older age, high-risk disease initially, and had initial CNS III status, were at higher risk of developing acute CNS complications during their treatment period. Patients who developed visual disturbances were associated with unfavorable outcomes. Despite that, around 80% of patients showed complete recovery, but still, 15% of them died from these complications.
Iron Overload in Children With Leukemia; Identification of a Cutoff Value for Serum Ferritin Level
Authors: Zekavat Omid Reza , Fallah Tafti Farima , Bordbar Mohammadreza , Parand Shirin , Haghpanah Sezaneh
Published: December 2023

Objective:

To determine the prevalence of iron overload in children with acute lymphoblastic leukemia (ALL) after treatment cessation and establish a cutoff value for serum ferritin level as an indicator of iron overload.

Background:

Early detection and monitoring of iron overload in patients with leukemia is crucial.

Methods:

In this prospective cohort study, 66 pediatric patients with ALL who were treated at a tertiary referral center affiliated with Shiraz University of Medical Sciences in Shiraz, Southern Iran, were investigated from July 2020 to December 2022. Serum ferritin levels were measured 6 months after treatment completion. T2* magnetic resonance imaging of the liver and heart was done for all patients. The receiver operating characteristic curve was used to illustrate the area under the receiver operating characteristic curve to assess the diagnostic value of serum ferritin level and total transfusion volume.

Results:

A total of 24 patients (36.4%) had iron overload in the heart or liver based on T2 magnetic resonance imaging findings. Serum ferritin level was a highly accurate diagnostic marker for iron overload in pediatric patients with ALL, with a sensitivity of 95.8%, and specificity of 85.7% for a cutoff value of 238.5 ng/mL. Also, blood transfusion was a good predictor of iron overload a sensitivity of 75% and specificity of 81% for a cutoff value of 28.3 mL/kg.

Conclusion:

We identified specific cutoff values for serum ferritin and blood transfusion volume to predict iron overload with high sensitivity and specificity. These markers offer a cost-effective and accessible approach for periodic screening of iron deposition, particularly in resource-constrained settings.
Palliative Care for Infants in the Neonatal Intensive Care Unit
Authors: Kim Eun Sook , Kim Sue , Kim Sanghee , Kim Sujeong , Ahn So Yoon , Lee Hyejung
Published: December 2023

This scoping review aimed to explore the characteristics of neonatal palliative care in the neonatal intensive care unit, including the features, contents, and experiences of infants, parents, and nurses during palliative care. Five databases (PubMed, Cochrane, CINAHL, Research Information Sharing Service, and Korean Studies Information Service System) were searched to identify relevant articles published between 2011 and 2020. From the systematic search and review process, 13 studies that met the eligibility criteria were selected for the analysis. From the literature review, 2 key principles were found to facilitate neonatal palliative care: family-centered care and integrative care in the neonatal intensive care unit. In addition, the themes found in this review included (1) providing comfortable care to dying infants with respect to infants and offering parents choices, (2) therapeutic communication, (3) support with respect, and (4) bereavement care for parents of dying infants in the neonatal intensive care unit. Caregivers require effective communication, manpower support, emotional support, educational programs, and well-defined protocols. The evidence mapped and synthesized in this review indicates the need to facilitate the provision of palliative care in the neonatal intensive care unit in line with the unique needs of infants, parents, and nurses.
Concordance of human papillomavirus genotypes in mailed home-based self-collected versus clinician-collected anal swabs among sexual and gender minority individuals
Authors: Nitkowski Jenna , Giuliano Anna R. , Ridolfi Tim , Chiao Elizabeth , Fernandez Maria E. , Schick Vanessa , Swartz Michael D. , Smith Jennifer S. , Nyitray Alan G.
Published: December 2023

Background

Home-based self-sampling may be a viable option for anal cancer screening among sexual minority men (SMM). Yet limited research has compared home-based self-collected with clinician-collected anal swabs for human papillomavirus (HPV) genotyping.

Methods

The Prevent Anal Cancer Self-Swab Study recruited SMM and transgender persons 25 years and over in Milwaukee, Wisconsin, USA to participate in an anal cancer screening study. Participants were randomized to a home or clinic arm. Home-based participants were mailed an anal self-sampling kit to complete and return via postal mail. They were also asked to attend a clinic appointment where a clinician collected an anal swab. Swabs were HPV-genotyped using the SPF10-LiPA25 assay. We analyzed 79 paired self and clinician swabs to determine HPV prevalence, percent agreement, and sensitivity and specificity of the mailed home-based anal self-swab to detect HPV genotypes using the clinician-collected swab as the reference.

Results

The median number of days between the home and clinic swab was 19 days (range = 2 to 70). HPV was detected in 73.3% of self and 75.0% of clinician anal swabs (p = .99). Prevalence of any HPV, any high-risk HPV, any low-risk HPV, and individual HPV types did not significantly differ between self and clinician anal swabs. Agreement between self and clinician swabs was over 90% for 21 of the 25 HPV genotypes. Mailed home-based self-collected swabs had a sensitivity of 94.1% (95% CI: 82.9 – 99.0) for detection of high-risk HPV versus clinician-collected sampling.

Conclusions

Mailed home-based self-collected and clinician-collected anal swabs demonstrated high concordance for HPV genotyping.
Unmet Needs for HIV Ancillary Services Among Persons With Diagnosed HIV Aged 55 years and Older
Authors: Byrd Kathy K. , Buchacz Kate , Crim Stacy M. , Beer Linda , Lu Jen-Feng , Dasgupta Sharoda
Published: December 2023

Background:

Approximately 2 in 5 persons with HIV (PWH) in the United States are aged 55 years or older. HIV ancillary services, such as case management and transportation services, can help older PWH remain engaged in care. We used data from the Medical Monitoring Project (MMP) to describe the prevalence of unmet needs for ancillary services among persons with diagnosed HIV aged 55 years or older.

Setting:

MMP is an annual cross-sectional study that reports representative estimates on adults with diagnosed HIV in the United States.

Methods:

We used MMP data collected during June 2019–May 2021 to calculate weighted percentages of cisgender men and cisgender women with HIV aged 55 years or older with unmet needs for ancillary services, overall and by selected characteristics (N = 3200). Unmet need was defined as needing but not receiving a given ancillary service. We assessed differences between groups using prevalence ratios (PRs) and 95% confidence intervals with predicted marginal means.

Results:

Overall, 37.7% of cisgender men and women with HIV aged 55 years or older had ≥1 unmet need for ancillary services. Overall, 16.6% had ≥1 unmet need for HIV support services, 26.9% for non-HIV medical services, and 26.7% for subsistence services. There were no statistically significant differences in unmet needs for services by gender. The prevalence of ≥1 unmet need was higher among non-White persons (PR range: 1.35–1.63), persons who experienced housing instability (PR = 1.70), and those without any private insurance (PR range: 1.49–1.83).

Conclusion:

A large percentage of older PWH have unmet needs for ancillary services. Given the challenges that older PWH face related to the interaction of HIV and aging-associated factors, deficits in the provision of ancillary services should be addressed.
Factors Associated With COVID-19 Vaccination Among Racial/Ethnic Minority Groups With HIV in South Florida
Authors: Ramírez-Ortiz Daisy , Jean-Gilles Michele , Sheehan Diana M. , Ladner Robert , Li Tan , Trepka Mary J.
Published: December 2023

Background:

Racial/ethnic minority groups with HIV in the United States are particularly vulnerable to COVID-19 consequences and can significantly benefit from increased uptake of COVID-19 vaccines. This study identified factors associated with full COVID-19 vaccination among people with HIV.

Setting:

Ryan White HIV/AIDS Program in Miami-Dade County, FL.

Methods:

Data were collected from 299 Ryan White HIV/AIDS Program adult clients during January–March 2022 using a cross-sectional phone survey. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). All analyses were weighted to be representative of the race/ethnicity and sex distribution of clients in the Ryan White HIV/AIDS Program.

Results:

Eighty-four percent of participants were fully vaccinated with a primary vaccine series; stratified by race/ethnicity, the percentages were 88.9% of Hispanic, 72.0% of black/African American, and 67.5% of Haitian participants. Fully vaccinated participants were less likely to be black/African American than Hispanic (aOR = 0.18; 95% CI: 0.05 to 0.67) and more likely to not endorse any misconceptions about COVID-19 vaccines (aOR = 8.26; 95% CI: 1.38 to 49.64), to report encouragement to get vaccinated from sources of information (aOR = 20.82; 95% CI: 5.84 to 74.14), and to perceive that more than 50% of their social network was vaccinated (aOR = 3.35; 95% CI: 1.04 to 10.71). Experiences of health care discrimination, structural barriers to access vaccines, and recommendations from HIV providers were not associated with full vaccination.

Conclusions:

These findings highlight the importance of delivering accurate and positive messages about vaccines and engaging social networks to promote COVID-19 vaccination among people with HIV. This information can be leveraged to promote uptake of subsequent boosters and other recommended vaccines.
Associations Between Estimates of Arterial Stiffness and Cognitive Functioning in Adults With HIV
Authors: Jones Raymond , Jessee Matthew B. , Booker Robert , Martin Samantha L. , Vance David E. , Fazeli Pariya L.
Published: December 2023

Background:

Vascular aging, a precursor of arterial stiffness, is associated with neurocognitive impairment (NCI) and cardiovascular disease. Although HIV is associated with rapid vascular aging, it is unknown whether arterial stiffness mediates changes in cognitive function. We explored whether estimated markers of vascular aging were associated with NCI indices in HIV-positive individuals.

Methods:

This study was a secondary analysis of an observational study. Neurocognitive functioning was assessed using a battery of 7 domains (verbal fluency, executive functioning, speed of information processing, attention/working memory, memory [learning and delayed recall], and motor skills). Vascular aging was assessed using estimated markers of arterial stiffness (ie, estimated pulse wave velocity, pulse pressure, and vascular overload index). A multivariable regression adjusted for demographics, cardiovascular disease risk factors, and HIV clinical variables was used to examine the association between vascular aging and NCI outcomes.

Results:

Among 165 people with HIV, the mean age was 51.5 ± 6.9 years (62% men and 83% African American/Black or Other). In fully adjusted models, an increase in estimated pulse wave velocity and pulse pressure was associated with lower T scores in learning (−2.95 [−5.13, −0.77]) and working memory (−2.37 [−4.36, −0.37]), respectively. An increase in vascular overload index was associated with lower T scores in working memory (−2.33 [−4.37, −0.29]) and learning (−1.85 [−3.49, −0.21]).

Conclusions:

Estimated markers of arterial stiffness were weakly associated with neurocognitive functioning, suggesting that vascular aging may have a role in cognitive decline among people with HIV.
The effect of SGLT2 inhibitor on clinical outcomes in patients with type 2 diabetes and atrial fibrillation
Authors: Cho Yongin , Shin Sung-Hee , Park Min-Ae , Suh Young Ju , Park Sojeong , Jang Ji-Hun , Kim Dae-Young , Kim So Hun
Published: December 2023

Background

Sodium glucose cotransporter 2 (SGLT2) inhibitors improve clinical outcomes in several populations including type 2 diabetes, chronic renal insufficiency, and heart failure (HF). However, limited data exist on their effects on atrial fibrillation (AF).

Methods

We conducted a retrospective cohort study using the National Health Insurance Service database. A total of 4,771 patients with type 2 diabetes and AF who were newly prescribed SGLT2 inhibitors or DPP4 inhibitors were selected and matched in a 1:2 ratio by propensity score with 37 confounding variables. We assessed the effect of SGLT2 inhibitors on the composite outcome of either HF hospitalization or death compared with DPP4 inhibitors.

Results

Over a median follow-up of 31 months, patients on SGLT2 inhibitors were associated with a lower risk of hospitalizations for HF or mortality compared to those on DPP4 inhibitors (HR 0.61; 95% CI 0.44-0.85; P=0.004). SGLT2 inhibitor use was also associated with a lower risk of mortality (HR 0.61; 95% CI 0.39-0.94; P=0.025) and CV mortality (HR 0.43; 95% CI 0.21-0.86; P=0.018), but not of MI (HR 1.22 [95% CI 0.72-2.09]; P=0.461) or stroke (HR 1.00 [95% CI 0.75-1.33]; P=0.980). The incidence of hospitalizations for HF, although statistically insignificant, tended to be lower in the SGLT2 inhibitor group (HR 0.63 [95% CI 0.39-1.02]; P=0.062).

Conclusion

In a nationwide cohort of patients with type 2 diabetes and AF, SGLT2 inhibitor was associated with a lower risk of mortality compared to DPP4 inhibitor, which may suggest that SGLT2 inhibitors may be considered as the first-line antidiabetic medication in patients with type 2 diabetes and AF.
Women empowerment and utilization of HIV testing among couples in Zambia: Evidence from the Zambia Demographic and Health Survey 2018
Authors: Mbele Whiteson , Dako-Gyeke Phyllis , Ndapewa Frans Andreas , Ching Jordanne
Published: December 2023

In Zambia, women are disproportionally more affected by HIV compared to men. This has mainly been attributed to harmful gender norms that enhance male dominance and disempower women, preventing them from exercising their right to negotiate for safe sex and utilizing HIV prevention services such as HIV testing. This study examined associations between women’s empowerment and HIV testing among married and partnered women.

We analyzed secondary data from the couple’s recode of the 2018 Zambia demographic and health survey. Univariable and multivariable logistic regression analysis was conducted, and p<0.05 was considered statistically significant. We included a total of 5,328 married and partnered women in the analysis, of which 5057 (94.9%) had undergone an HIV test before. After adjusting for confounders, decision-making was the only independent predictor of HIV testing among measures of empowerment. Women who were highly empowered in decision-making were more likely to have undergone an HIV test compared to those who were lowly empowered (AOR = 2.1; 95% CI: 1.5, 2.9). Women aged 20-29 years (AOR = 2.4; 95% CI: 1.6, 3.6), 30-39 years (AOR = 5.3; 95% CI: 3.4, 8.2), or 40-49 years (AOR = 2.9; 95% CI: 1.9, 4.7), those with primary education (AOR = 2.4; 95% CI: 1.7, 3.4) or secondary and higher (AOR = 4.1; 95% CI: 2.3, 7.2), rich women (AOR = 2.4; 95% CI: 1.5, 3.7) or women with middle wealth (AOR = 1.5; 95% CI: 1.1, 2.2) and those who gave birth in the last 5 years (AOR = 3.3; 95% CI: 2.5, 4.5) were more likely to have been tested for HIV. This study highlights the critical influence of women’s empowerment in decision-making on HIV testing. Additionally, level of education, wealth, age, and having given birth before are essential factors to consider in promoting HIV testing among women in Zambia.
Human ASXL1 Deficiency Causes Epigenetic Dysfunction, Combined Immunodeficiency and EBV–Associated Hodgkin Lymphoma
Authors: Fu Maggie P , Sharma Mehul , Merrill Sarah M , Yousefi Pariya , Tan Ryan , Modi Bhavi P , Bel Kate Del , Deyell Rebecca J , Rozmus Jacob , Rehmus Wingfield , Hildebrand Kyla J , James Elliot , Blanchard-Rohner Géraldine , Lin Susan , Shopsowitz Kevin E , Setiadi Audi , Terry Jefferson , Lee Anna F , Drögemöller Britt I , Matthews Allison , Tarailo-Graovac Maja , Sauvé Laura , Mitchell Hana , Prendiville Julie S , MacIsaac Julie L , Dever Kristy , Lin David T S , Meijer Mandy , Ross Colin J D , Dobson Simon R M , Vercauteren Suzanne M , Wasserman Wyeth W , van Karnebeek Clara D M , McKinnon Margaret L , Kobor Michael S , Turvey Stuart E , Biggs Catherine M
Published: December 2023

Inborn errors of immunity (IEI) are a group of disorders caused by deleterious variants in immune-related genes, including some that function as epigenetic regulators. Additional sex combs-like 1 (ASXL1) is an epigenetic modifier that has not previously been linked to an IEI. SomaticASXL1variants are found in clonal hematopoiesis and hematologic neoplasms, while heterozygous germline variants cause Bohring–Opitz syndrome. We present a new IEI caused by biallelic germline variants inASXL1. The patient had a complex and unusual history of disease progression notable for persistent cutaneous vaccine-strain rubella granulomas initially manifesting in early childhood, chronic macrocytosis and mild bone marrow cellular hypoplasia, and Epstein Barr virus– associated Hodgkin lymphoma in adolescence. Detailed immunophenotyping revealed progressive loss of B-cells, hypogammaglobinemia, and T-cell lymphopenia with severe skewing toward a memory phenotype and elevated expression of T-cell exhaustion and senescence markers. Molecular investigations confirmed ASXL1 protein deficiency in the patient’s T-cells and fibroblasts. The T-cells exhibited marked loss of DNA methylation, increased epigenetic aging, and CD8 T-cell dysfunction. These aberrations were ameliorated by lentivirus-mediated transduction with wild-typeASXL1, confirming the pathogenicity ofASXL1variants. This study defines a novel human IEI caused by ASXL1 deficiency, a diagnosis that should be considered in individuals with chronic viral infections, virus-associated hematologic malignancies, and combined immunodeficiency. Furthermore, our findings provide fresh insights into the mechanisms underlying the roles of human ASXL1 in T-cell function as well as in the development and maintenance of lymphomas.
Harmonic patterns embedding ictal EEG signals in focal epilepsy: new insight into the epileptogenic zone
Authors: Hu Lingli , Ye Lingqi , Ye Hongyi , Liu Xiaochen , Xiong Kai , Zhang Yuanming , Zheng Zhe , Jiang Hongjie , Chen Cong , Wang Zhongjin , Zhou Jiping , Wu Yingcai , Huang Kejie , Zhu Junming , Chen Zhong , Ding Meiping , Yang Dongping , Wang Shuang
Published: December 2023

The EEG biomarkers for identifying epileptogenic zone (EZ) need further refinement. Through time-frequency analysis, we identified a unique ictal spectral structure, referred to as the “harmonic pattern” (H pattern), during seizure onset or propagation in stereo-EEG signals of focal epilepsy patients. The H pattern, observed within specific EEG segments, often appeared simultaneously across different brain regions at a consistent fundamental frequency, highlighting a crucial stage in seizure propagation characterized by inter-regional synchronization. The dominant H pattern, which is identified as those above the third quartile of band numbers, demonstrated greater nonlinearity compared to the non-dominant H pattern, as evidenced by bispectral analysis. The waveforms associated with the dominant H pattern were more stereotyped and showed increased skewness and/or asymmetry. Remarkably, the complete removal of areas exhibiting the dominant H pattern was independently associated with favorable surgical outcomes. The H pattern provides unique insights into ictal neural dynamics and introduces a novel approach for measuring the EZ over an extended time window.

Impact statement

Hu et al. report that this distinct nonlinear spectral feature signifies a stereotyped waveform change and identifies a ‘uniform frequency component’ within the ictal network as a key stage of seizure propagation.
LMNAR644C associates with hepatic steatosis in a large cohort and increases cellular lipid droplet accumulationin vitro
Authors: Upadhyay Kapil K. , Du Xiaomeng , Chen Yanhua , Speliotes Elizabeth K. , Brady Graham F.
Published: December 2023

The R644C variant of lamin A is controversial, as it has been linked to multiple phenotypes in familial studies, but has also been identified in apparently healthy volunteers. Here we present data from a large midwestern US cohort showing that this variant associates genetically with hepatic steatosis, and with related traits in additional publicly available datasets, whilein vitrotesting demonstrated that this variant increased cellular lipid droplet accumulation. Taken together, these data support thisLMNAvariant’s potential pathogenicity in lipodystrophy and metabolic liver disease.
Isolating transdiagnostic effects reveals specific genetic profiles in psychiatric disorders
Authors: Keser Engin , Liao Wangjingyi , Allegrini Andrea G. , Rimfeld Kaili , Eley Thalia C. , Plomin Robert , Malanchini Margherita
Published: December 2023

Evidence indicates a great degree of genetic overlap between psychiatric diagnoses. Accounting for these transdiagnostic effects can sharpen research on disorder-specific genetic architecture. Here we isolate genetic effects that are shared across 11 major psychiatric disorders (p factor) to gain further insight into genetic specificity and comorbidity over and above that contributed by the p factor, unique to each psychiatric disorder. After adjusting for transdiagnostic genetic effects, we examined genetic correlations among psychiatric traits as well as relationships with other biobehavioural traits. The landscape of genetic associations between pairs of psychiatric disorders changed substantially, and their genetic correlations with biobehavioural traits showed greater specificity. Isolating transdiagnostic genetic effects across major psychiatric disorders provides a nuanced understanding of disorder-specific genetic architecture and genetic comorbidity, and may help guide diagnostic nomenclature and treatment research.
Macular Oxygen Saturation in Glaucoma Using Retinal Oximetry of Visible Light Optical Coherence Tomography
Authors: Wang Jingyu , Sadlak Natalie , Fiorello Marissa G. , Desai Manishi , Yi Ji
Published: December 2023

Purpose

Oxygen saturation (sO2) plays a critical role in retinal pathophysiology, especially at the macula, which undergoes significant energy consumption. While macular damage has been suggested to be involved in early-stage glaucoma, there has been no report to date on non-invasive macular sO2in glaucoma. Therefore, we conducted this study to compare macular sO2associated with other clinical measurements between normal and glaucoma subjects and evaluate whether there are significant differences.

Method

This is a cross-sectional study. We used visible light optical coherence tomography (VIS-OCT) for retinal oximetry in perifoveal vessels. The subjects from groups of normal, suspect/pre-perimetric glaucoma (GS/PPG) and perimetric glaucoma (PG) were scanned using VIS-OCT in the macular region with a sampling density of 512×256 in an area of 5×5 mm2. 48 eyes (16 normal, 17 GS/PPG and 15 PG) were included for the analysis. For each eye, we measured the sO2of arterioles (AsO2), venules (VsO2), and calculated the difference between arterioles and venules (A-V sO2=AsO2-VsO2), oxygen extraction (OE=(AsO2-VsO2)/AsO2×100%). Additionally, we included Zeiss Cirrus OCT scans and 24-2 visual field test (VFT) for clinical benchmark. One-way ANOVA was used to compare the differences among the three groups. Spearman correlation tests were used for correlation sO2markers to standard metrics including the thickness of ganglion cell layer and inner plexiform layer (GCL+IPL), circumpapillary retinal nerve fiber layer (cpRNFL) and mean deviation (MD) in VFT.

Result

Significant differences were found among three groups for all VIS-OCT, Zeiss OCT, and VFT variables. Macular AsO2, A-V sO2, OE decreased, and VsO2increased along with severity. Macular AsO2and A-V sO2were statistically correlated with GCL+IPL and cpRNFL in all eyes, as well as only PG eyes. Within PG eyes, the correlation between AsO2and GCL+IPL is dominant in more damaged lower hemifield.

Conclusion

The GS/PPG and PG subjects had significantly higher macular VsO2, lower A-V sO2and OE indicating less oxygen consumption. The sO2measured by retinal oximetry of VIS-OCT can be a potential metric for the early diagnosis of glaucoma.