bluuebunny/crossref_metadata_2025 huggingface dataset:
Definition of Progressive Keratoconus: A Systematic Review
Authors: Henriquez Maria A. , Larco Carolina , Izquierdo Luis
Published: December 2024

Purpose:

To identify the definitions used for progressive keratoconus in the literature.

Methods:

A systematic literature review aimed to identify the definitions used for “progressive keratoconus” in the published articles. A comprehensive search from January 2018 to May 2023 was conducted across Cochrane Library, PubMed, Taylor & Francis, Web of Science, and other bibliographic databases at Oftalmosalud, Lima, Peru. The inclusion criteria were articles including patients with keratoconus without any previous surgical procedure and containing the definition of “progressive keratoconus” or “keratoconus progression” and a sample size greater than 10 eyes.

Results:

A total of 221 articles were included for analysis. The 3 most frequent parameters to define progression included data from anterior curvature, pachymetry, and refraction used in 97.8% (216/221), 37.6% (83/221), and 32.1% (71/221) of the articles, respectively. Specifically, the most frequent criterion used was maximum keratometry (Kmax), used in 85.5% (189/221) of the articles. Progression was assessed between 6- and 12-month follow-up in 64.7% (143/221) of the articles. Data from posterior cornea were used in only 8.1% (18/221) of the studies. None of the studies included data from the corneal epithelium.

Conclusions:

The present study demonstrates the lack of unified criteria to define progression of keratoconus and an underutilization of the technology described. It also shows that the single point Kmax measurement is the most commonly used criterion, followed by a change in refractive astigmatism and thinning at the thinnest pachymetric point.
Impact of citrus fruit and hesperidin intake on multiple health outcomes: An umbrella review
Authors: Cheng Yu-Sen , Zhou Yong
Published: December 2024

Citrus fruits are rich sources of several biologically active flavonoids such as hesperidin, naringin, and polymethoxylated flavones. We evaluated the evidence of associations between citrus fruit or hesperidin intake and multiple health outcomes. An umbrella review was conducted for studies performed in humans. Overall, 246 articles were initially identified by searching in 4 databases. Twenty-two meta-analyses and systematic reviews with 28 health outcomes met the inclusion criteria. Citrus fruit intake had beneficial effects on all-cause mortality (relative risk [RR]. 0.90; 95% confidence interval [95% CI], 0.86 to 0.94), cardiovascular diseases (RR, 0.78; 95% CI, 0.66 to 0.92), coronary heart disease (RR, 0.91; 95% CI, 0.86 to 0.96), stroke (RR, 0.74; 95% CI, 0.65 to 0.84), type 2 diabetes mellitus (RR, 0.85; 95% CI, 0.78 to 0.92), and several cancers. Dose-response analyses indicated that each 100-g/d increase in citrus fruit intake could reduce the risks of all-cause mortality by 6% (RR, 0.94; 95% CI, 0.88 to 1.00), stroke by 22% (RR, 0.78; 95% CI, 0.69 to 0.90), and cardia gastric cancer by 40% (RR, 0.60; 95% CI, 0.44 to 0.83). Citrus fruit intake also had beneficial effects on the lipid profile and body weight control (weighted mean difference, −1.28; 95% CI, −1.82 to −0.74). Grapefruits could reduce the systolic blood pressure (weighted mean difference, −2.43, 95% CI, −4.77 to −0.09). Hesperidin supplementation significantly improved inflammation. Citrus fruit intake was generally safe and beneficial for multiple health outcomes in humans. However, grapefruit and pomelo juice may affect the bioavailability of various medications, so care should be exercised before increasing the intake of these fruits or their juices.
Exfoliative esophageal bleeding caused by blind placement of a nasogastric tube: Two cases and a literature review
Authors: Huang Qi-Qiang , Wei Jing-Jing , Zhuang Ze-Hao
Published: December 2024

Transnasal intubation is a clinical operation usually performed blindly at the bedside. Mild adverse events, such as epistaxis and tube misplacement, are relatively common. Esophageal bleeding or perforation and other serious adverse events are rare. In the present study, two cases of severe diffuse esophageal bleeding caused by the blind placement of a nasogastric tube are described. These cases were successfully treated using a covered metal stent or Sengstaken-Blakemore tube. A review of the literature regarding the possible causes of such adverse events and the potential endoscopic treatments for severe hemorrhage are discussed.
Association between the nutritional status and radiation pharyngeal mucositis in patients with head and neck cancer during radiotherapy: A longitudinal study
Authors: Zhang Li-Chuan , Wang Yu-Jie , Zhuang Bing , Zhang Tong , Jin San-Li , Wan Meng , Zhao Dan , Zheng Bao-Min , Xiao Shao-Wen , Liu Wei-Xin , Xu Xiao-Long , Huang Zhou , Sun Yan , Zhang Ya-Ru , Wang Wei-Hu , Lu Qian
Published: December 2024

Objective

Radiation mucositis, especially pharyngeal mucositis, severely affects the oral intake of patients of head and neck cancer (HNC) during radiotherapy. Whether the nutritional status affects the severity of pharyngeal mucositis is currently unknown. This study investigated the incidence of malnutrition and radiation pharyngeal mucositis in patients with HNC during radiotherapy and analyzed the impact of the nutritional status on radiation pharyngeal mucositis.

Methods

Consecutive patients with HNC receiving radiotherapy were recruited for this longitudinal observational study. Data were collected at baseline (T1), midtreatment (T2), and at the end of treatment (T3). The Common Terminology Criteria for Adverse Events version 4.0 and the Global Leadership Initiative on Malnutrition criteria were used to assess pharyngeal mucositis and the nutritional status, respectively.

Results

There were 348 HNC patients who completed all assessments. The pharyngeal mucositis of patients with HNC was aggravated during radiotherapy (χ
2 = 553.521, P < 0.001). At T3, 56.0% of patients had moderate or severe pharyngeal mucositis. The proportion of patients with malnutrition increased significantly during treatment (21.3% at T1 vs 46.8% at T2 vs 76.1% at T3, χ
2 = 209.768, P < 0.001). Both a multivariable analysis of generalized estimating equations and a logistic regression analysis showed that pharyngeal mucositis was associated with malnutrition.

Conclusions

Malnutrition was common in patients with HNC during radiotherapy, and it was closely related to pharyngeal mucositis. Joint interventions targeting nutrition and symptom management should be considered for patients with HNC.
Role of selenium in cell death
Authors: Gao Peng-Ning , Wang Chuan-Lin , Xu Jia-Li , Liu Shan-Ling , Zhou Lan
Published: December 2024

Selenium is an essential nutrient closely related to redox homeostasis in the body. A redox imbalance will adversely affect the microenvironment inside and outside the cell, leading to cell death. Various types of cell death have been discovered in recent years, but the role(s) of selenium and the associated mechanism(s) of action require further elaboration. We review the roles and mechanisms of action of selenium in cell necrosis, apoptosis, ferroptosis, autophagy, and pyroptosis. Under normal conditions, selenium inhibits cell necrosis, apoptosis, ferroptosis, autophagy, and pyroptosis by downregulating the nuclear factor κB pathway, upregulating antiapoptotic proteins, decreasing oxidative stress, increasing antioxidant enzyme activity, enhancing the mTOR pathway, and downregulating the NLRP3/caspase-1 pathway, thereby helping to maintain the normal physiological functions of cells. On the other hand, selenium deficiency leads to activation of the PI3K/AKT and Notch/Hes1 pathways, causing a significant increase in the level of oxidative stress in the organism, resulting in cell necrosis, apoptosis, and pyroptosis. In the case of malignancy, the in vivo metabolite of inorganic selenium, hydrogen selenide, plays an antitumor role by inducing apoptosis and ferroptosis in tumor cells because of its high redox activity. In conclusion, an adequate level of selenium in the body is essential for maintaining normal cellular physiological functions and reducing fibrotic alterations. Furthermore, the in vivo metabolites of inorganic selenium may have some clinical value in antitumor therapy.
Value of combining the serum d-lactate, diamine oxidase, and endotoxin levels to predict gut-derived infections in cancer patients
Authors: Yang Shou-Mei , Zhang Xiao-Dan , Ma Huai-Xing , Wu Dan , Liu Xing , Yu Hao-Bin , Li Shi-Wei , Gao Wen-Jun , Liu Wei-Wei , Li Su-Yi
Published: December 2024

Objective

This is a retrospective observational cohort study. The objective of this retrospective observational cohort study was to evaluate the value of the combined serum d-lactic acid, diamine oxidase (DAO), and endotoxin levels to predict intestinal barrier impairment and gut-derived infection (GDI) in cancer patients.

Methods

Cancer patients receiving chemotherapy or palliative care treatment at our hospital were enrolled in the study. The serum concentrations of DAO, d-lactic acid, and endotoxin were determined using the intestinal barrier function biochemical index analysis system. The patients' infection information came from the hospital's Medicom Prescription Automatic Screening System and the medical records. Three hundred fifty-three cancer patients were included in the study (53.8% female, 73.7% cancer stage IV, 27.8% had bowel obstruction).

Results

The total incidence of GDI was 33.4% (118/353). The median length of hospital stay was 16 days for patients with GDI, compared with 7 days for patients without GDI (P < 0.001). The media hospitalization costs were ¥27,362.35 for patients with GDI compared with ¥11,614.08 for patients without GDI (P < 0.001). The serum concentrations of DAO, d-lactic acid, and endotoxin were significantly higher in patients with GDI. As malignant bowel obstruction (MBO) worsened, the concentrations of DAO, d-lactic acid, and endotoxin increased. Multivariate logistic regression models revealed that the DAO, endotoxin, IL-6, and C-reactive protein levels were significantly associated with an increased risk of GDI. In addition, we also found a fivefold increased risk of infection in patients with MBO compared with those without bowel obstruction (OR = 6.210, P < 0.001). All of the areas under the receiver operating characteristic curve (AUCs) for DAO, d-lactate, and endotoxin to predict GDI were <0.7 (AUC = 0.648, P < 0.001; AUC = 0.624, P < 0.01; AUC = 0.620, P < 0.01, respectively). However, when the parameters were combined (DAO + d-lactate + endotoxin), the predictive power increased significantly (AUC = 0.797, P < 0.001). Moreover, combining these intestinal barrier indicators and the presence of MBO had better power to predict GDI than either alone (AUC = 0.837, P < 0.001).

Conclusions

Combining the serum DAO, d-lactic acid, and endotoxin levels was a better predictor of GDI than any of the indicators alone, and combining these with the diagnosis of MBO could further improve the efficacy for predicting GDI.
Serum albumin as a prognostic predictor reflecting host immunity in patients with non–small cell lung cancer
Authors: Li Ling-Yu , Sun Hai-Shuang , Chen Xiao , Xu Dong-Sheng , Chen Nai-Fei , Guo Han-Fei , Han Wei , Yan Xu , Guo Fei-Fei , Li Jia-Xuan , Zeng Tan-Lun , Li Wen-Qian , Cui Jiu-Wei
Published: December 2024

Objective

Serum albumin (ALB) can transport nutrients to circulating and local immune cells by passing through blood vessels and has attracted attention as a prognostic predictor of non–small cell lung cancer (NSCLC) because it reflects the host immunity from peripheral blood (PBL) to the tumor microenvironment.

Methods

Clinical data regarding the PBL and tumor tissues were obtained at The First Hospital of Jilin University between February 2009 and March 2017. We detected indices of glucose and lipid metabolism, classified and counted PBL lymphocytes using flow cytometry, determined the tumor-infiltrating lymphocytes by quantitative immunofluorescence, and analyzed the T-cell receptor (TCR) repertoire by high-throughput sequencing of the TCR β-chain. The correlations between ALB and metabolic immune indices were analyzed by t tests and Pearson chi-square test.

Results

A total of 211 enrolled NSCLC patients were divided into a relatively high-ALB group (> 41.75 g/L, n = 56) and a low-ALB group (≤ 41.75 g/L, n = 155); patients with high ALB had lower Treg cells (P < 0.05) and more CD8+ cytotoxic T cells in the PBL (P < 0.01) and a higher proportion of stromal CD8+ tumor-infiltrating lymphocytes (P = 0.047) than patients with low ALB. High ALB was also significantly related to more diversity in the TCR repertoire (P = 0.0021, r
2 = 0.5481). Moreover, ALB was identified as an independent prognostic factor based on a multivariate Cox regression analysis (P = 0.032; hazard ratio (HR) = 1.804; 95% confidence interval (CI) = 1.035–3.146). The median overall survival in patients with low ALB vs high ALB was 28.2 vs 42.2 months (P = 0.0142), respectively. Among patients with nonmetastatic NSCLC (stage I-III), there was a higher incidence of distant metastasis in the low-ALB group than that in the high-ALB group (41.3% and 22.2%, P = 0.043). A low ALB also had a strong association with a higher risk for disease progression (P < 0.001) and death (P < 0.01; HR = 0.555; 95%
CI = 0.312–0.988).

Conclusions

Albumin could affect the host immunity, and high ALB predicted a reduced risk of distant metastasis and improved the prognosis in NSCLC patients.
Application of medium-chain fatty acids in metabolic diseases
Authors: Yu Yang , Miao Ming-Yong , Zhang Jie
Published: December 2024

Medium-chain fatty acids (MCFAs), which are important dietary fats, can be rapidly metabolized to efficiently produce a high amount of energy owing to their unique transportation system. MCFAs have thus become high-value functional foods. MCFAs also have antibacterial and immunoregulatory effects, help to maintain intestinal health, and have shown benefits for disease prevention and treatment. Therefore, they have the potential to be used for a variety of purposes. We herein describe the metabolic pathways involving MCFAs and their main biological functions in the human body. In addition, the effects of MCFAs as adjuvant therapy for different diseases, such as obesity, polycystic ovary syndrome, sarcopenia, and malignancy are summarized, and the likely mechanisms of action are discussed. Finally, we describe possible future clinical applications of MCFAs in the field of metabolic diseases.
“Share the Fear”: Communication Concerns of Parents With Cancer With Dependents and Coparents: A Qualitative Needs Assessment Study
Authors: Caparso Cinzia , Bowen Zoe , Choi Sung Won
Published: December 2024

Background

The estimated 1.6 million adults in the United States with cancer who also have dependents face unique challenges given the profound impact of cancer on their families, such as increased psychological distress, decreased quality of life, and altered family functioning. Unfortunately, little is known about the mutual cancer-related communication concerns from the perspectives of the parents with cancer or the coparents. Coparents care for the patient and dependents until they reach adulthood (eg, unmarried, divorced, stepparent, and/or same-sex partnerships).

Objective

To understand the mutual cancer-related communication concerns from the perspectives of parents with cancer and the coparents and intervention delivery preferences.

Methods

Fifteen parents with cancer and 15 coparents were recruited to participate in semistructured interviews between October 2022 and September 2023 within an academic medical center in Midwestern states. Interviews were conducted via Zoom. The data were analyzed through Charmaz’s inductive grounded theory approach.

Results

Parents with cancer and the coparents desire communication assistance with each other about discussing the cancer diagnosis with dependents, end-of-life planning, managing finances, and addressing mental health concerns and emotions. The majority of participants reported interest in a virtually delivered intervention.

Conclusions

Findings from this study provide a mutual understanding of cancer-related communication concerns from the perspectives of parents with cancer and the coparents.

Implications for Practice

These findings provide awareness for providers and the foundation to inform a web-based communication intervention about cancer-related concerns to promote family resiliency in this population, which provides a resource for providers to utilize.
Basilar Dolichoarteriopathy and Early Clinical Deterioration in Acute Isolated Pontine Infarction
Authors: Oge Dogan D. , Arsava Ethem M. , Topcuoglu Mehmet A.
Published: December 2024

Objectives:

Early clinical worsening (ECW) in acute isolated pontine infarcts (AIPI) is frequent, associated with poor prognosis, and its predictors have not been adequately clarified. A possible role of dolichoectatic basilar artery (BA) anatomy in ECW in patients with AIPI is herein studied.

Methods:

In 146 AIPI patients, infarcts were grouped into tegmental, lateral, anterolateral, anteromedial horizontally; and low, mid, mid-up, and upper pontine vertically. BA dolichoectasia was categorized according to Smoker criteria. An additional criteria of BA laterality angle was described. The length between the infarct long-axis and BA cross-sectional center was measured, and named as “branch length (BL).” ECW was defined as any increase in NIHSS.

Results:

ECW was seen in 22 (15%) patients. Univariate analysis documented a higher female ratio (22% vs. 10%, P=0.007), higher atrial fibrillation (18% vs. 7%, P=0.067), more common anteromedial infarct location (77% vs. 49%, P=0.025), and Smoker category-3 BA height (32% vs. 10%, P=0.043) in these patients. In anteromedial infarcts, BL was longer (8.3 vs. 6.1 mm, P=0.052), and reaching to significance in those located at mid-up/upper pontine level (1.22 vs. 0.62 mm, P=0.006). BL >4.4 mm showed an acceptable discriminatory capacity for ECW with an AUC of ROC: 0.615 (95% CI: 0.511-0.712). A regression model indicated female sex (β±SE=1.129±0.551, P=0.040), BL (per 4.4 mm, β±SE=1.236±0.614, P=0.044), and BA height-category-3 (β±SE=1.711±0.645, P=0.008) as independent predictors for ECW.

Conclusions:

Some features of basilar dolichoarteriopathy, such as the extreme location of the height of the BA tip and the length of the involved perforator in the prepontine cistern, may be predictors of early clinical worsening in acute isolated pontine infarcts.
Pineal Gland Activity in Advanced-Stage Pediatric Neuroblastoma Patients on 68Ga-DOTATATE PET/CT
Authors: Isik Emine Goknur , Denizmen Dilara , Arslan Dilşad Fırat , Simsek Duygu Has , Özkan Zeynep Gözde
Published: December 2024

Neuroblastoma is the most common malignancy in infants and the most common extracranial solid tumor accounting for approximately 6% of pediatric cancer. Although surgical intervention serves as the primary treatment for early-stage disease, advanced-stage cases necessitate a variety of oncologic therapeutic approaches, including 131I-MIBG and peptide receptor radionuclide therapy. Herein we report incidental pineal gland activity, represented in 68Ga-DOTATATE PET/CT (SSTR-PET) in 3 pediatric patients diagnosed with stage 4 neuroblastoma, related to the physiological distribution of radiopharmaceuticals.
Factors Influencing Fronto-Orbital Relapse in Patients With Syndromic Craniosynostosis: A 2 Decade Review
Authors: Moshal Tayla , Lasky Sasha , Roohani Idean , Stanton Eloise W. , Jolibois Marah I. , Wolfe Erin M. , Urata Maya , Munabi Naikhoba C.O. , Hammoudeh Jeffrey A. , Urata Mark M.
Published: December 2024

Fronto-orbital retrusion may occur after primary surgical correction of craniosynostosis, particularly in patients with syndromic craniosynostosis. This study investigated reoperation rates and factors contributing to FO relapse among this cohort. A retrospective review evaluated reoperation for FO relapse in patients with syndromic multisuture craniosynostosis who underwent primary fronto-orbital advancement (FOA) + calvarial vault remodeling (CVR) at our institution between 2004 and 2024. Revision surgeries included repeat FOA or monobloc advancement/distraction. FOA advancement distance was measured using postoperative computed tomography and Mimics software. ROC analysis evaluated the accuracy of FOA distance in predicting subsequent FO relapse. Conditional margins identified optimal advancement distances. Logistic regression of predictors of FO relapse adjusted for age at surgery, craniofacial syndrome, posterior vault distraction osteogenesis (PVDO), advancement distance, and postoperative helmet therapy. Fifty-two patients underwent a mean of 2.8±1.9 skeletal craniofacial procedures each. With a mean follow-up time of 9.2±6.5 years, 16 (30.8%) patients required reoperation for FO relapse. Larger advancement distances were the sole significant predictor of relapse, increasing the odds by 49.6% (OR 1.496, 95% CI: 1.085–2.063; P=0.014). Relapse rates were lower with advancements ≤17.2 mm (0.0%) than with further advancements (42.0%, P=0.002). Specifically, advancements >18.8 mm were associated with significantly higher relapse rates (P<0.05). Almost one-third of patients with multisuture syndromic craniosynostosis underwent FO region readvancement. Advancements <17.2 mm during initial FOA appeared to mitigate relapse, while advancing beyond 18.8 mm may increase the risk. Investigation of additional protective factors against FO relapse is encouraged to minimize surgical burden.
Functional Vision Questionnaire Detects Near Triad Impairments in Adolescent Athletes With Concussion History
Authors: Leinonen Jouko , Mikkola Roosa , Peltonen Kati , Hokkanen Laura , Laitala Tiina
Published: December 2024

Background:

Concussions are mild traumatic brain injuries that often cause vision problems. They have significant impacts on everyday life, cognitive capacity, and sports performance, and may affect injury prevalence in fast contact sports such as ice hockey. A functional vision questionnaire specifically designed for sports was used here to study the correlation between vision problems and concussion history.

Methods:

In this national cross-sectional concussion study, 860 Finnish elite-level male adolescent ice hockey players (aged 13–21 years) answered a functional vision questionnaire and performed a computerized neurocognitive test, ImPACT. Totally 265 athletes reported a history of at least 1 concussion. All data were statistically compared with age-matched athletes with no concussion history (n = 595). For further analysis, athletes were divided into subgroups by age and number of previous concussions.

Results:

Previously concussed athletes reported more general and eye-specific symptoms than their healthy controls. Increases in eye fatigue, frontal headaches, and blinking were statistically significant. Also statistically more problems with depth perception and evaluating distances, concentration problems, blurred vision, and losing the object in sight were observed among athletes with concussion history.

Conclusions:

Concussion history reflects an increase in the prevalence of vision deficits, as determined by multiple disturbances in the near triad. The significant number of vision problems in the concussion history groups strongly suggests that functional vision should routinely be evaluated in athletes. The vision problems observed in the athletes with concussion history may indicate an increased injury risk that should be addressed.
Frequency & Relationship between Loneliness and Smartphone Addiction among Medical Students of Lahore
Authors: Sohail Ammar
Published: December 2024

Smartphone addiction is a widespread and concerning issue wherein individuals excessively and compulsively use their smartphones. It’s characterized by habitual and prolonged phone usage, resulting in negative impacts on physical and mental health, strained personal relationships, increased fixation on the device, and a notable decrease in both personal productivity and overall quality of life. This study aims to find relationship between smartphone addiction and loneliness & prevalence of loneliness and smartphone addiction among medical students in Pakistan. This will also help to gauge the extent of related health issues and will lead to formulation of better guidelines for people suffering from smartphone addiction & loneliness thus improving the social and mental wellbeing of people from all age groups in Pakistani society.
Sociodemographic and Behavioral Factors Associated with Diet Quality among Low-income Community Health Center Patients with Hypertension
Authors: Cheng Jessica , Faulkner Katherine C , Malone Ashlie , Gu Kristine D. , Thorndike Anne N
Published: December 2024

Objective

Identify the most important sociodemographic and behavioral factors related to the diet of low-income adults with hypertension in order to guide the development of a community health worker (CHW) healthy eating intervention for low-income populations with hypertension.Design:In this cross-sectional analysis, dietary recalls were used to assess Healthy Eating Index-2020 (HEI-2020) total (range: 0 to 100 [best diet quality]) and component scores and sodium intake. Self-reported sociodemographic and behavioral data were entered into a Least Absolute Shrinkage and Selection Operator (LASSO) regression model to determine the relative importance of factors related to diet quality.

Setting

Five community health centers in Boston, Massachusetts.

Participants

Adults (>20 years old) with a hypertension diagnosis.

Results

Participants (N=291) were mostly female (65.0%), on Medicaid (82.8%), food insecure (59.5%), and Hispanic (52.2%). The mean (95% CI) HEI-2020 score was 63.0 (62.3, 65.7) Component scores were low for sodium and whole grains; mean (SE) sodium intake was 2676.9 (45.5) mg/day. The most important factors associated with lower HEI-2020 scores were: not having own housing, male gender, tobacco use, marijuana use, and skipping meals; the most important factors associated with higher HEI-2020 scores were Hispanic ethnicity and receipt of community food resources (5-fold cross-validated R2=0.17).

Conclusions

In this population of low-income adults with hypertension, diet quality would be improved by reducing sodium and increasing whole grain intake. Healthy eating interventions among low-income populations should consider providing dietary guidance in the context of behavioral factors (e.g., meal skipping) and substance use (e.g., marijuana) and should address barriers to health eating through referral to community food resources (e.g., food pantries).
Hyperorality in Frontotemporal Dementia: How Psychiatric and Neural Correlates Change Across the Disease Course
Authors: Morrow Christopher B. , Onyike Chiadi , Pantelyat Alexander , Smith Gwenn S. , Leoutsakos Jeannie , Faria Andreia V. , Graff-Radford Neill R. , Darby R. Ryan , Ghoshal Nupur , Staffaroni Adam M. , Rascovsky Katya , Miyagawa Toji , Balaji Akshata , Tsapkini Kyrana , Lapid Maria I. , Mendez Mario F. , Litvan Irene , Pascual Belen , Rojas Julio C. , Wszolek Zbigniew K. , Domoto-Reilly Kimiko , Kornak John , Kamath Vidyulata
Published: December 2024

Objectives

Hyperorality is one of the core features of behavioral variant frontotemporal dementia (bvFTD), however, the cognitive, psychiatric, and neuroanatomic correlates of hyperorality across disease stages remain unclear. This study works to fill this knowledge gap by exploring these associations in the early and advanced stages of bvFTD.

Methods

Participants with sporadic and genetic bvFTD were enrolled in the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium (ALLFTD). The primary analyses used baseline data to compare cognitive and psychiatric symptoms in those with and without hyperorality stratified by disease severity. Linear multivariable regressions adjusting for age and total intracranial volume were used to examine baseline associations between regional gray matter volumes and hyperorality status. Five anatomic regions of interest were pre-selected for analysis based on previously identified neuroanatomic correlates of hyperorality in bvFTD.

Results

Hyperorality was present in 50% of early-stage bvFTD participants (n = 136) and was associated with higher rates of ritualistic/compulsive behavior. Hyperorality was present in 63% of advanced-stage participants (n = 208) and was associated higher rates of apathy, and ritualistic/compulsive behavior. Regional gray matter volumes were similar in those with and without hyperorality in early-stage participants. In the advanced-stage participants, hyperorality was associated with lower gray matter volumes in the right dorsal and ventral striatum.

Conclusions

Hyperorality emerges early in bvFTD and is accompanied by deficits in social cognition and complex-ritualistic behavior prior to clinically significant gray matter volume loss. These findings suggest that early identification and treatment of hyperorality could improve neuropsychiatric trajectories in bvFTD.
Laser Ablation of Periventricular Nodular Heterotopia for Medically Refractory Epilepsy
Authors: McCormack Ryan M. , Chandran Arjun S , Lhatoo Samden D. , Pati Sandipan , Li Zhouxuan , Harris Katherine , Lacuey Nuria , Kalamangalam Giridhar , Thompson Stephen , Tandon Nitin
Published: December 2024

Objective

Periventricular Nodular Heterotopia (PVNH) is the most common neuronal heterotopia, frequently resulting in pharmaco-resistant epilepsy. PVNH has a deep location which renders localization of seizure onsets and traditional surgical therapy challenging and of limited success. Here we characterize variables that predict good epilepsy outcomes following surgical intervention using SEEG-informed MRgLITT.

Methods

A prospectively compiled surgical epilepsy database from a single high-volume epilepsy referral center was used to identify patients who underwent SEEG evaluation for PVNH and characterize the intervention on outcomes.

Results

Thirty-nine patients underwent SEEG-informed MRgLITT. Associated imaging abnormalities— mesial temporal sclerosis (MTS) or polymicrogyria (PMG) were treated based on SEEG.

SEEG-guided MRgLITT of the seizure onset zone (SoZ) in PVNH and associated epileptic tissue was carried out. PVNH and PMG were densely sampled—mean 16.5(SD=2)/209.4(SD=36.9) SEEG probes/recording contacts. A single trajectory was used in 18, two in 13, and three or more in eight patients. Volumetric analyses revealed a high percentage of PVNH SoZ ablation (96.6%, SD=5.3%) in unilateral and bilateral (92.9%, SD=7.2%) cases. Mean follow-up duration was 31.4 months (SD=20.9). Seizure freedom was excellent overall: unilateral PVNH without other imaging abnormalities—80%; PVNH with MTS or PMG—63%; Bilateral PVNH—50%. SoZ ablation percentage significantly impacted surgical outcomes (p<0.001).

Interpretation

PVNH plays a central role in seizure genesis. MRgLITT represents a transformative technological advance in PVNH-associated epilepsy with seizure control outcomes consistent with those seen in focal lesional epilepsies. In localized unilateral cases and otherwise normal imaging, performing PVNH ablation without invasive recordings may be reasonable.
A Mixed-Methods Investigation of Coping, Adaptation and Health-Related
Quality of Life in Individuals Experiencing Endometriosis
Authors: Moore Chloe , Cogan Nicola , Williams Lynn
Published: December 2024

Objectives

Endometriosis is associated with reduced health-related quality of life
(HRQoL). Coping has been linked to HRQoL in this population but longitudinal
research to establish the impact of coping on HRQoL over time is lacking.
Additionally, limited research has examined coping and adaptation to
endometriosis from an in-depth qualitative or mixed-methods perspective.
Therefore, adopting a mixed-methods approach, the current research aimed to
investigate how individuals experiencing endometriosis coped and adapted to
their condition, and the extent to which coping predicted HRQoL over
time.

Design

A sequential, mixed-methods design incorporating a two-wave longitudinal
survey and semi-structured interviews.

Methods

408 UK-based participants diagnosed with endometriosis completed the
baseline survey, measuring demographics, clinical factors, and coping with
283 completing the follow-up survey assessing HRQoL a year later. Data was
analysed through hierarchical regression analysis. Meanwhile, 30
semi-structured interviews were conducted and analysed using reflexive
thematic analysis. Findings were integrated by considering points of
convergence, divergence, and complementarity between the datasets.

Results

Analysis of the quantitative data indicated an enduring impact of coping
on HRQoL. Avoidant strategies and endometriosis-related information-seeking
predicted reduced HRQoL, whilst trust in medical care exerted a protective
function. Three themes were constructed from the qualitative data:
disconnection from the body; balancing boundaries and self-care; and
empowered adaptation. Integration of the datasets emphasised the significant
impact of coping on HRQoL and wellbeing, revealing avoidance and positive
adaptation as prominently employed coping strategies.

Conclusions

The results position coping as an important therapeutic target in
endometriosis care, particularly through fostering empowerment and
adaptation to support HRQoL.
Orbitofrontal cortex hypergyrification in hallucinating schizophrenia patients: surface ratio as a promising brain biomarker
Authors: Núñez Christian , Stephan-Otto Christian , Roldán Alexandra , Grasa Eva Mª , Escartí Mª José , Aguilar García-Iturrospe Eduardo J. , García-Martí Gracián , de la Iglesia-Vaya Maria , Nacher Juan , Portella Maria J. , Corripio Iluminada
Published: December 2024

Background

There has been increasing interest in the study of brain gyrification in schizophrenia since it may provide additional useful information on the cytoarchitecture and connectivity of the brain. Various methods have been developed to estimate brain gyrification that, so far, have yielded mixed and inconclusive results in schizophrenia studies. To the best of our knowledge, an alternative method to compute brain gyrification, known as surface ratio (SR), has not yet been applied to a schizophrenia sample. Our aim in this study was to assess whether SR could provide new insights on the brain structure of schizophrenia patients and the severity of symptoms. We also computed a more established brain gyrification measure, namely absolute mean curvature (AMC), for comparison.

Method

We processed and analyzed a total of 63 magnetic resonance images, 25 from schizophrenia patients with treatment-resistant auditory verbal hallucinations (SCH-H), 18 from schizophrenia patients without hallucinations (SCH-NH), and 20 from healthy controls (HC). We estimated brain gyrification with SR and AMC employing CAT software.

Results

The SR measure mainly revealed that SCH-H patients had a more folded orbitofrontal cortex than SCH-NH patients and HC. Gyrification in this region was also negatively associated with positive symptoms, specifically with the delusions and conceptual disorganization items, only in the SCH-H group. Conversely, SCH-NH and HC showed more SR than SCH-H in other frontal areas. As for the AMC measure, we identified two areas where HC showed more gyrification than SCH-H patients, but no relationships arose with symptoms.

Discussion

We hypothesize that the hypergyrification of the orbitofrontal cortex displayed by SCH-H patients, as captured by the SR measure, suggests aberrant and/or excessive wiring in these patients, which in turn could give rise to auditory verbal hallucinations. Alternatively, we comment on potential compensatory mechanisms that may better explain the negative association between orbitofrontal gyrification and positive symptomatology. Importantly, the estimation of brain gyrification with the SR measure seems to capture the most relevant differences and associations, making it a promising biomarker in schizophrenia research.
The WHO Disease Outbreak News during the Covid-19 pandemic
Authors: Weets Ciara M. , Carlson Colin J. , Robertson Hailey , Toole Kate , McGivern Lauren , Graeden Ellie , Katz Rebecca
Published: December 2024

During the Covid-19 pandemic, the World Health Organization (WHO) was faced with the task of regular public updating—about both the pandemic itself, and hundreds or potentially thousands of other health emergencies. Here, we examined the 242 reports published in the WHO Disease Outbreak News (DON) during the first four years of the Covid-19 pandemic (2020 to 2023), and document the diseases and regions that were reported. We find that multinational epidemics of diseases like Ebola virus and MERS-CoV continue to dominate the DON. However, recent years have also seen more reports of climate-sensitive infectious diseases, as well as a state shift in influenza outbreak reporting in both China and the rest of the world. Surprisingly, the DON was only minimally used to document the Covid-19 pandemic and the global mpox epidemic, almost exclusively before the declaration of a public health emergency of international concern. Notably, inconsistent reporting related to Covid-19 variants of concern speaks to the ongoing evolution of the DON as a resource, and potentially, to its complicated relationship with international travel and trade restrictions. We suggest that researchers should continue to exercise caution when treating the DON as a global record of outbreak history, but that the DON is a compelling record of the WHO itself, including the process it uses to assess outbreak risk.
Sourcing Bivariate Genetic Overlap for Polygenic Prediction using MiXeR-Pred
Authors: Parker Nadine , Cheng Weiqiu , Hindley Guy F. L. , O’Connell Kevin S. , Parekh Pravesh , Hagen Espen , Smeland Olav B. , Djurovic Srdjan , Shadrin Alexey A. , Andreassen Ole A. , Frei Oleksandr , Dale Anders M.
Published: December 2024

The past two decades have seen the advent and mass application of genome-wide association studies (GWAS). The observation that complex phenotypes are polygenic has contributed to the development of the polygenic score (PGS) for understanding individual-level genetic predisposition. There have been substantial advances in PGS methodology in recent years. However, few methods leverage the pleiotropic nature of complex phenotypes for polygenic prediction. Here, we present MiXeR-Pred, a novel approach for polygenic prediction that builds on an established MiXeR framework to source genetic overlap with a secondary phenotype to inform PGS prediction of a primary phenotype. We apply MiXeR-Pred using both bipolar disorder and schizophrenia as complex primary phenotypes along with the following secondary phenotypes: education attainment, major depressive disorder, and measures of cortical brain morphology. We compare MiXeR-Pred predictions to the PGS derived from each primary phenotype’s GWAS in addition to the multi-trait analysis of GWAS (MTAG) approach, which can use correlated secondary phenotypes to boost discovery and prediction for a primary phenotype. We show that MiXeR-Pred improves prediction performance when compared to both the primary GWAS and MTAG PGS, regardless of the secondary phenotype. Not only can MiXeR-Pred be used to further our understanding of pleiotropy among complex phenotypes, but it also provides a novel conceptualization of how one can source pleiotropy to improve PGS performance which can ultimately contribute to advancements in personalized medicine. The MiXeR-Pred tool is available athttps://github.com/precimed/mixer-pred.
African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1
Authors: Jerez Pilar Álvarez , Wild Crea Peter A. , Ramos Daniel M. , Gustavsson Emil K. , Radefeldt Mandy , Makarious Mary B. , Ojo Oluwadamilola O. , Billingsley Kimberley J. , Malik Laksh , Daida Kensuke , Bromberek Sarah , Hu Carol , Schneider Zachary , Surapaneni Aditya L. , Stadler Julia , Rizig Mie , Morris Huw R. , Pantazis Caroline B. , Leonard Hampton L. , Screven Laurel , Qi Yue A. , Nalls Mike A. , Bandres-Ciga Sara , Hardy John , Houlden Henry , Eng Celeste , Burchard Esteban González , Kachuri Linda ,   Global Parkinson’s Genetics Program (GP2), Singleton Andrew B. , Fischer Steffen , Bauer Peter , Reed Xylena , Ryten Mina , Beetz Christian , Ward Michael , Okubadejo Njideka U. , Blauwendraat Cornelis
Published: December 2024

Recently, a novel African ancestry specific Parkinson’s disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant (rs3115534-G) is carried by ∼50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups, but is almost absent in European and Asian ancestry populations.GBA1is a gene of high clinical and therapeutic interest. Damaging bi-allelic protein-coding variants cause Gaucher disease and mono-allelic variants confer risk for PD and Dementia with Lewy Bodies, likely by reducing the function of glucocerebrosidase. Interestingly, the novel African ancestry specificGBA1risk variant is a non-coding variant, suggesting a different mechanism of action. Using full length RNA transcript sequencing, we identified intron 8 expression in risk variant carriers (G) but not in non-variant carriers (T). Antibodies targeting the N-terminus of glucocerebrosidase showed that this intron-retained isoform is likely not protein coding and subsequent proteomics did not identify a shorter protein isoform, suggesting the disease mechanism is RNA-based. CRISPR editing of the reported index variant (rs3115534) revealed that this is the responsible sequence alteration driving production of these intron 8 containing transcripts. Follow-up analysis of this variant showed that it is in a key intronic branchpoint sequence and therefore has important implications in splicing and disease. In addition, when measuring glucocerebrosidase activity we identified a dose-dependent reduction in risk variant carriers (G). Overall, we report the functional effect of aGBA1non-coding risk variant, which acts by interfering with the splicing of functionalGBA1transcripts, resulting in reduced protein levels and reduced glucocerebrosidase activity. This understanding reveals a novel therapeutic target in an underserved and underrepresented population.
Inconsistent Music-Based Intervention Reporting in Dementia Studies: A Systematic Mapping Review
Authors: Lepping Rebecca J. , Hess Benjamin J. , Taylor Jasmine M. , Hanson-Abromeit Deanna , Williams Kristine N.
Published: December 2024

Recent research has shown beneficial results for music-based interventions (MBIs) for persons living with Alzheimer’s disease and related dementias (AD/ADRD), but reports often lack sufficient detail about the MBI methodology, which reduces replicability. A detailed checklist for best practices in how to report MBIs was created in 2011 by Robb and colleagues to remedy the lack of detail in MBI descriptions. The implementation of the checklist specifically in AD/ADRD research has not been established. Given the complexity of music and the variety of uses for research and health, specific MBI descriptions are necessary for rigorous replication and validation of study results.

This systematic mapping review utilized the “Checklist for Reporting Music-Based Interventions” to evaluate the current state of MBI descriptive specificity in AD/ADRD research. Research articles testing MBIs and reviews of MBI efficacy published between January 2015 and August 2023 were scored using the checklist and the results were summarized. Nineteen studies were screened, and reporting was inconsistent across the 11 checklist criteria. Six out of 19 studies fully reported more than 5 of the 11 criteria. Only one of the 11 scoring criteria was at least partially reported across all 19 studies.

Thorough reporting of intervention detail for MBIs remains limited in AD/ADRD MBI research. This impedes study validation, replication, and slows the progress of research and potential application of music in practice. Greater implementation of the reporting guidelines provided by Robb and colleagues would move the field of MBI research for AD/ADRD forward more quickly and efficiently.
Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution
Authors: Pisanic Nora , Antar Annukka A. R. , Hetrich Marissa K. , Demko Zoe O. , Zhang Xueyan , Spicer Kristoffer , Kruczynski Kate L. , Detrick Barbara , Clarke William , Knoll Maria Deloria , Thomas David L. , Dawood Fatimah S. , Veguilla Vic , Karron Ruth A. , Manabe Yukari C. , Heaney Christopher D.
Published: December 2024

High priority efforts are under way to support the development of novel mucosal COVID-19 vaccines, such as the US Government’s ProjectNextGenand the Center for Epidemic Preparedness Innovations’ (CEPI) goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how the immunogenicity of mucosal vaccines will be evaluated. This study investigated the role of oral mucosal antibody responses in viral clearance and in COVID-19 symptom duration.

Participants with PCR-confirmed SARS-CoV-2 infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for RT-PCR and symptom information at up to eight follow-ups from April 2020 to February 2022.

High and moderate oral fluid anti-spike (S) SIgA post infection was associated with significantly higher likelihood of viral clearance and of COVID-19 symptom resolution across age groups. Those with high and moderate anti-S SIgA cleared the virus and recovered 14 days (95% CI: 10-18 days) and 9-10 days (95% CI: 6-14 days) earlier, respectively. Delayed but higher oral fluid anti-S IgG was associated with significantly longer time to viral clearance and recovery. The effect size of moderate or high SIgA was equivalent to prior COVID-19 vaccine immunity, which was also associated with faster clearance and recovery. Unvaccinated adults with prolonged COVID-19 symptoms had significantly lower anti-RBD SIgA 15-30 days after infection onset (p<0.001).

Robust mucosal SIgA early post infection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new vaccines that can boost local mucosal immunity.

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.