bluuebunny/crossref_metadata_2025 huggingface dataset:
LONG-HOSP Score: A Novel Predictive Score for Length of Hospital Stay in Acute Lower Gastrointestinal Bleeding – A Multicenter Nationwide Study
Authors: Fujita Minoru , Aoki Tomonori , Manabe Noriaki , Ito Yoichiro , Kobayashi Katsumasa , Yamauchi Atsushi , Yamada Atsuo , Omori Jun , Ikeya Takashi , Aoyama Taiki , Tominaga Naoyuki , Sato Yoshinori , Kishino Takaaki , Ishii Naoki , Sawada Tsunaki , Murata Masaki , Takao Akinari , Mizukami Kazuhiro , Kinjo Ken , Fujimori Shunji , Uotani Takahiro , Sato Hiroki , Suzuki Sho , Narasaka Toshiaki , Hayasaka Junnosuke , Funabiki Tomohiro , Kinjo Yuzuru , Mizuki Akira , Kiyotoki Shu , Mikami Tatsuya , Gushima Ryosuke , Fujii Hiroyuki , Fuyuno Yuta , Gunji Naohiko , Toya Yosuke , Narimatsu Kazuyuki , Nagaike Koji , Kinjo Tetsu , Sumida Yorinobu , Funakoshi Sadahiro , Kobayashi Kiyonori , Matsuhashi Tamotsu , Komaki Yuga , Miki Kuniko , Watanabe Kazuhiro , Ayaki Maki , Murao Takahisa , Suehiro Mitsuhiko , Shiotani Akiko , Hata Jiro , Haruma Ken , Kaise Mitsuru , Nagata Naoyoshi
Published: August 2023

Introduction: Length of stay (LOS) in hospital affects cost, patient quality of life, and hospital management; however, existing gastrointestinal bleeding models applicable at hospital admission have not focused on LOS. We aimed to construct a predictive model for LOS in acute lower gastrointestinal bleeding (ALGIB). Methods: We retrospectively analyzed the records of 8,547 patients emergently hospitalized for ALGIB at 49 hospitals (the CODE BLUE-J Study). A predictive model for prolonged hospital stay was developed using the baseline characteristics of 7,107 patients and externally validated in 1,440 patients. Furthermore, a multivariate analysis assessed the impact of additional variables during hospitalization on LOS. Results: Focusing on baseline characteristics, a predictive model for prolonged hospital stay was developed, the LONG-HOSP score, which consisted of low body mass index, laboratory data, old age, nondrinker status, nonsteroidal anti-inflammatory drug use, facility with ≥800 beds, heart rate, oral antithrombotic agent use, symptoms, systolic blood pressure, performance status, and past medical history. The score showed relatively high performance in predicting prolonged hospital stay and high hospitalization costs (area under the curve: 0.70 and 0.73 for derivation, respectively, and 0.66 and 0.71 for external validation, respectively). Next, we focused on in-hospital management. Diagnosis of colitis or colorectal cancer, rebleeding, and the need for blood transfusion, interventional radiology, and surgery prolonged LOS, regardless of the LONG-HOSP score. By contrast, early colonoscopy and endoscopic treatment shortened LOS. Conclusions: At hospital admission for ALGIB, our novel predictive model stratified patients by their risk of prolonged hospital stay. During hospitalization, early colonoscopy and endoscopic treatment shortened LOS.
Busulfan for Allogeneic Hematopoietic Stem Cell Transplantation in Children with Severe Aplastic Anemia: A Retrospective Study
Authors: Si Yingjian , Luo Rongmu , Qin Maoquan , Du Zhenlan , Zhang Xiaomei , Wang Ya , Chen Wei , Gu Wenjing , Xing Guosheng , Dou Lingsong , Cao Wei , Feng Zhichun
Published: August 2023

Introduction: This retrospective study aimed to compare a range of conditioning regimens in children with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the Seventh Medical Center of PLA General Hospital between January 2008 and June 2017. Methods: Patients were categorized into the Bu (Bu + Flu + Cy + ATG-F regimen) and control (Flu + Cy + ATG-F) groups, with a median follow-up time after HSCT of 3.5 (range, 3.1–6.2) and 3.7 (3.2–5.9) years in the Bu and control groups, respectively. Results: No differences were observed between the two groups regarding the median time of peripheral blood neutrophil and platelet engraftment (p = 0.538 and p = 0.491); the 28-day engraftment rates of neutrophils were similar (p = 0.199), although higher for platelets with Bu (p = 0.044). Additionally, graft failure was 0% and 20.0% in the Bu and control groups, respectively (p = 0.004). In both groups, the incidence of grades III–IV (or grades II–IV) acute graft-versus-host disease (GVHD) and chronic GVHD was not significantly different (p > 0.05). Moreover, the 3-year overall survival and failure-free survival did not show significant differences (p = 0.670 and p = 0.908). Discussion: In children with SAA undergoing allo-HSCT, conditioning regimen with Bu + Flu + Cy + ATG-F is capable of enhancing the myeloablation effect, promoting donor hematopoietic stem cell engraftment, and reducing the graft failure rate. Furthermore, it does not increase the incidence of complications, including GVHD.
Use of Polynomial Reference Ranges for Atrioventricular Intervals Assessed by Fetal Echocardiography in Anti-Ro/SSA Antibody-Positive Pregnancies to Exclude Fetal Heart Blocks: A Pilot Study
Authors: Mosimann Beatrice , Amylidi-Mohr Sofia , Surbek Daniel , Förger Frauke , Raio Luigi
Published: August 2023

Introduction: Maternal anti-Ro/SSA antibodies can cause fetal atrioventricular blocks (AVB). This pilot study aims to apply previously published echocardiographic reference ranges of the fetal atrioventricular (AV) intervals in the setting of anti-Ro/SSA antibody-positive pregnancies in order to exclude a 1° AVB. Materials and Methods: Between January 2018 and September 2022, we included all women with known anti-Ro/SSA antibodies followed up at the prenatal ultrasound department of the University Hospital of Bern. AV intervals were serially measured by two previously reported methods and plotted against previously created reference ranges. Results: We included 23 pregnancies from 17 anti-Ro/SSA antibody-positive women with connective tissue diseases. 443 AV interval measurements were recorded between 16+3 and 38+4 weeks of gestation. 14 (3.2%) AV-intervals measured >150 ms, none measured >170 ms and 8 (1.8%) were found to be >95th percentile. In none of the pregnancies, serial AV-prolongations were noted. The postnatal electrocardiograms demonstrated normal sinus rhythm without AVB in all children. Conclusion: AV intervals of pregnancies followed up for anti-Ro/SSA antibodies without neonatal AVB lie within our published polynomial reference ranges. While diagnosing a 1° AVB remains controversial, more data are needed to prove that our reference ranges are helpful exclude a 1° AVB.
Genome-Wide Association Studies for Albuminuria of Nondiabetic Taiwanese Population
Authors: Yang Wei-shun , Chuang Gwo-Tsann , Che Tony Pan-Hou , Chueh Li-Yun , Li Wen-Yi , Hsu Chih-Neng , Hsiung Chia-Ni , Ku Hsiao-Chia , Lin Yi-Ching , Chen Yi-Shun , Hee Siow-Wey , Chang Tien-Jyun , Chen Shiau-Mei , Hsieh Meng-Lun , Lee Hsiao-Lin , Liao Karen Chia-Wen , Shen Chen-Yang , Chang Yi-Cheng
Published: August 2023

Introduction: Chronic kidney disease, which is defined by a reduced estimated glomerular filtration rate and albuminuria, imposes a large health burden worldwide. Ethnicity-specific associations are frequently observed in genome-wide association studies (GWAS). This study conducts a GWAS of albuminuria in the nondiabetic population of Taiwan. Methods: Nondiabetic individuals aged 30–70 years without a history of cancer were enrolled from the Taiwan Biobank. A total of 6,768 subjects were subjected to a spot urine examination. After quality control using PLINK and imputation using SHAPEIT and IMPUTE2, a total of 3,638,350 single-nucleotide polymorphisms (SNPs) remained for testing. SNPs with a minor allele frequency of less than 0.1% were excluded. Linear regression was used to determine the relationship between SNPs and log urine albumin-to-creatinine ratio. Results: Six suggestive loci are identified in or near the FCRL3 (p = 2.56 × 10−6), TMEM161 (p = 4.43 × 10−6), EFCAB1 (p = 2.03 × 10−6), ELMOD1 (p = 2.97 × 10−6), RYR3 (p = 1.34 × 10−6), and PIEZO2 (p = 2.19 × 10−7). Genetic variants in the FCRL3 gene that encode a secretory IgA receptor are found to be associated with IgA nephropathy, which can manifest as proteinuria. The PIEZO2 gene encodes a sensor for mechanical forces in mesangial cells and renin-producing cells. Five SNPs with a p-value between 5 × 10−6 and 5 × 10−5 are also identified in five genes that may have a biological role in the development of albuminuria. Conclusion: Five new loci and one known suggestive locus for albuminuria are identified in the nondiabetic Taiwanese population.
Urgent versus Non-Urgent Transcatheter Aortic Valve Implantation Outcomes
Authors: Castelo Alexandra , Teixeira Bárbara , Grazina André , Mendonça Tiago , Rodrigues Inês , Garcia Brás Pedro , Ferreira Vera Vaz , Ramos Rúben , Fiarresga António , Cruz Ferreira Rui , Cacela Duarte
Published: August 2023

Introduction: There are limited data about the outcomes of nonelective transcatheter aortic valve implantation (TAVI). Some studies suggest that these patients (pts) have worst results. Our purpose was to compare outcomes in pts submitted to urgent versus elective TAVI. Methods: Retrospective analysis of 298 consecutive pts submitted to TAVI between 2018 and 2021 in a single tertiary center. Baseline characteristics and outcomes were collected and compared between elective and nonelective TAVI. Results: Pts submitted to urgent TAVI (79 pts) had worse baseline characteristics, with higher EuroScore risk (9.26 vs. 5.17%, p < 0.0001), STS score (7.09 vs. 4.4%, p < 0.0001), and NT pro-natriuretic peptide B (10,168 vs. 3,241 pg/mL, p = 0.001), lower left ventricle ejection fraction (45 vs. 52%, p = 0.003), more diabetes (46.8 vs. 32.4%, p = 0.0.22), peripheral artery disease (21.5 vs. 6.8%, p < 0.0001), and poor vascular accesses (18.4 vs. 7.4%, p = 0.007). Urgent TAVI was associated with higher mortality (25.3 vs. 15.1%, p = 0.043), 30-day cardiovascular mortality (17.5 vs. 4%, p = 0.001), life-threatening bleeding (11.5 vs. 4.1%, p = 0.018), vascular complications (11.5 vs. 4.6%, p = 0.031), and longer hospital stay (28 vs. 12 days, p < 0.0001), but not with intensive care unit or post-TAVI hospital stay (5 vs. 4 days, p = 0.197 and 11 vs. 10 days, p = 0.572). When adjusted to differences in baseline characteristics, urgent TAVI was only associated with longer hospital stay (p < 0.0001). Conclusion: Pts submitted to urgent TAVI have worse short-term outcomes, but this seems to be attributable to the worse baseline characteristics instead of the urgent nature of the procedure.
A Heterozygous Variant of FGF13 Caused X-Linked Developmental and Epileptic Encephalopathy 90 in a Chinese Family
Authors: Cheng Haiying , Miao Pu , Wang Ye , Guo Yufan , Gao Liuyan , Lou Yuting , Yang Fan , Liang Mengmeng , Feng Jianhua
Published: August 2023

Developmental and epileptic encephalopathy (DEE) refers to a group of severe epilepsy encephalopathy and development disorders, and its typical clinical features include seizures, drug resistance, and developmental delay or regression. To date, limited studies have reported DEEs driven by FGF13. Here, we reported a girl with developmental and epileptic encephalopathy 90 caused by variant of FGF13. Her electroencephalogram (EEG) showed discontinuous hypsarrhythmia, and a heterozygous nonsynonymous variant in FGF13 [NM_004114.4: c.5C>G, p.(Ala2Gly)] was identified from the proband. The variant was not reported in public databases such as gnomAD and Exome Aggregation Consortium (ExAC), and was predicted to be damaging to proteins and classified as likely pathogenic according to the ACMG guidelines. The seizure was finally controlled by a combination of ACTH + zonisamide (10 mg/kg.d) + levetiracetam (52 mg/kg.d) + clonazepam (0.7 mg/kg.d).
Markers of Kidney Tubule Dysfunction and Major Adverse Kidney Events
Authors: Bullen Alexander L. , Fregoso Alma , Ascher Simon B. , Shlipak Michael G. , Ix Joachim H. , Rifkin Dena E.
Published: August 2023

Background: Serum creatinine and albuminuria are primary markers of glomerular function and injury, respectively. Tubular secretion, acid-base homeostasis, protein reabsorption, among other tubular functions, are largely ignored. This mini-review aimed to discuss how two tubular functions, secretion, and acid-base homeostasis are associated with major adverse kidney events (MAKEs). Summary: Proximal tubular secretion is an essential function that allows the elimination of endogenous substances and drugs. Recently discovered endogenous markers in urine and plasma allow a noninvasive way of assessing tubular secretion markers. Several studies have found an association between these markers and a higher risk of chronic kidney disease (CKD) progression and mortality. In a study we recently performed among patients with CKD and at risk of cardiovascular events, lower tubular secretion was associated with an increased risk of acute kidney injury and metabolic acidosis, independent of baseline eGFR and albuminuria. The kidney tubules also play a crucial role in acid-base homeostasis. Although the standard clinical assessment of acidosis consists of measuring serum bicarbonate, urinary ammonium excretion decreases before over metabolic acidosis. Urinary ammonium excretion is associated with CKD progression, a higher risk of kidney failure, and an increased mortality risk, independent of baseline eGFR and albuminuria. Key Messages: Novel biomarkers of kidney tubular health consistently associate with MAKEs, above and beyond baseline eGFR, albuminuria, and other CKD risk factors. Tubular markers may provide new opportunities to improve kidney prognosis, drug dosing, and monitoring for adverse events.
Histopathologic Follow-Up of Women with Inadequate ThinPrep™ Cervical Pap Tests and Positive High-Risk Human Papillomavirus Test Results
Authors: Kir Gozde , Ozen Suleyman
Published: August 2023

Introduction: We found only a few studies that had performed high-risk human papillomavirus (hrHPV) analyses of inadequate ThinPrep™ Papanicolaou (Pap) tests. Therefore, this study aimed to analyze unsatisfactory ThinPrep Pap tests using hrHPV tests. The colposcopic biopsy results of cases with an unsatisfactory ThinPrep Pap test and positive hrHPV results were revealed. Methods: Between January 1, 2018, and October 31, 2022, 965 (3.7%) of 25,958 liquid-based cytology specimens were evaluated as unsatisfactory. Ninety-five (9.8%) of 965 patients were positive for hrHPV. The colposcopic evaluation was performed in 28 (29.4%) of 95 patients, in whom 23 tests were adequate. Results: Twenty-three colposcopy biopsy results showed that 17 (73.9%) of 23 patients had benign biopsy results. High-grade squamous intraepithelial lesions were observed in three (13%) of the 23 patients, and low-grade squamous intraepithelial lesions were observed in two (8.6%) of the 23 patients. One of the 23 (4.3%) patients had keratinized squamous cell carcinoma of the cervix diagnosed histologically, although no tumor was visible upon gynecologic examination. Conclusion: For the management of unsatisfactory Pap tests, The American Society for Colposcopy and Cervical Pathology (ASCCP) recommends repeat cytology within 2–4 months. Evaluation of such patients using hrHPV tests may triage those with squamous intraepithelial lesions, even invasive cervical cancer. More studies with a larger number of cases are needed to analyze the hrHPV status and biopsy follow-up of cases with unsatisfactory cytology.
Efficacy of Blue LED Phototherapy on Sleep Quality and Behavioral and Psychological Symptoms of Dementia: A Double-Blind Randomized Controlled Trial
Authors: Chen Ying-Ren , Huang Wen-Yu , Lee Tso-Ying , Chu Hsin , Chiang Kai-Jo , Jen Hsiu-Ju , Liu Doresses , Chen Ruey , Kang Xiao Linda , Lai Yueh-Jung , Chou Kuei-Ru
Published: August 2023

Introduction: People with dementia often experience behavioral and psychological symptoms of dementia (BPSD), which are a major cause of caregiver burden and institutionalization. Therefore, we conducted a double-blind, parallel-group randomized controlled trial to examine the efficacy of blue-enriched light therapy for BPSD in institutionalized older adults with dementia. Methods: Participants were enrolled and randomly allocated into blue-enriched light therapy (N = 30) or the conventional light group (N = 30) for 60 min in 10 weeks with five sessions per week. The primary outcome was sleep quality measured by actigraphy and Pittsburgh Sleep Quality Index (PSQI). The secondary outcome was overall BPSD severity (Cohen-Mansfield Agitation Inventory [CMAI] and Neuropsychiatric Inventory [NPI-NH]). The outcome indicators were assessed at baseline, mid-test, immediate posttest, 1-month, 3-month, and 6-month follow-up. The effects of the blue-enriched light therapy were examined by the generalized estimating equation model. Results: Blue-enriched light therapy revealed significant differences in the objective sleep parameters (sleep efficiency: β = 5.81, Waldχ2 = 32.60, CI: 3.82; 7.80; sleep latency: β = −19.82, Waldχ2 = 38.38, CI:−26.09; −13.55), subjective sleep quality (PSQI: β = −2.07, Waldχ2 = 45.94, CI: −2.66; −1.47), and overall BPSD severity (CMAI: β = −0.90, Waldχ2 = 14.38, CI: −1.37; −0.44) (NPI-NH: β = −1.67, Waldχ2 = 30.61, CI: −2.26; −1.08) compared to conventional phototherapy immediate posttest, 1-month, 3-month, and 6-month follow-up. Furthermore, the effects for sleep efficiency and sleep latency lasted for up to 6 months. In the subscale analysis, the differences of the behavioral symptoms changed significantly between the groups in physical/nonaggressive (CI: −1.01; −0.26) and verbal/nonaggressive (CI: −0.97; −0.29). Conclusions: Blue-enriched light therapy is a feasible low-cost intervention that could be integrated as a comprehensive therapy program for BPSD among older adults with dementia.
Vocal Problems and Burnout Syndrome in Nonuniversity Teachers in Galicia, Spain
Authors: García-Real Teresa J. , Díaz-Román Tomás M. , Mendiri Paula
Published: August 2023

Introduction: Voice disorders and burnout syndrome are common among teachers. This study aimed to explore the relationship among vocal problems, burnout syndrome, and some personal work factors. Methods: This cross-sectional descriptive study enrolled 90 nonuniversity teachers who completed the Multidimensional Vocal Scale for Teachers (EVM-D) to evaluate vocal problems and an adapted Spanish version of the Maslach Burnout Inventory-Educators Survey (MBI-ES) to detect burnout syndrome. Results: Overall, 16% of teachers expressed symptoms compatible with burnout, and 60% of them were in the interval above the 75th percentile of the EVM-D, i.e., they had a high risk of vocal problems. An association between burnout and more vocal problems was established among teachers, particularly between the vocal symptoms and vocal abuse dimensions with the emotional exhaustion subscale of the MBI-ES. A history of anxiety/depression and fewer years of professional experience were associated with more vocal problems. The burnout group perceived more “loss of vocal power,” “vocal fatigue,” “vocal effort,” and “hoarseness.” Vocal abuse items received the highest scores of EVM-D. However, only “shouting” in the classroom was significantly different between the groups with and without burnout. Conclusion: Emotional exhaustion of burnout syndrome, history of anxiety/depression, and a shorter professional experience were associated with vocal problems, which could limit the performance of teachers. Reducing classroom noise, establishing strategies to avoid shouting, or strengthening personal accomplishments in teachers could be useful in breaking the cycle of vocal problems and emotional exhaustion, particularly at the beginning of their professional experience.
Evaluating the Impact of Obesity and Different Metabolic Statuses on the Prognosis of Hospitalized Patients with Inflammatory Bowel Disease: A Cohort Study
Authors: Wang Yanyan , Liu Luna , Han Junming , Fan Xiude , Guo Qingling , Wu Zhongming
Published: August 2023

Introduction: Obesity is associated with an increased risk of inflammatory bowel disease (IBD), whereas not all obese individuals have the same effect. In individuals with obesity, the role of metabolic status in the readmission of IBD remains unclear. Our study aimed to evaluate the association between different obesity metabolic phenotypes and the prognosis of IBD patients. Methods: We conducted a longitudinal cohort study using Nationwide Readmissions Database (NRD) (2018 sample). Out of 12,928,231 discharge records, 63,748 records with a discharge diagnosis of IBD were identified for analysis. Cox proportional hazard ratio (HR) with 95% confidence interval (CI) was calculated, adjusting for potential confounders. Results: During a 180-day follow-up in IBD patients with different obesity metabolic phenotypes, all-cause readmission rate, inpatient mortality rate, unplanned readmission rate, total charge, hospitalized length of stay were statistically different (all p < 0.001). After multivariate Cox regression analysis, IBD patients with metabolically unhealthy nonobese (MUNO) had higher risk of readmission (all-cause and unplanned) (HR 1.04, 95% CI: 1.00–1.08 and HR 1.06, 95% CI: 1.02–1.10), and those with metabolically unhealthy obesity (MUO) had higher risk of unplanned readmission (HR 1.08, 95% CI: 1.02–1.15). In subgroup analysis, both the MUNO group and MUO group had higher risk of readmission (all-cause and unplanned) in the ulcerative colitis (UC) subgroup, but only the MUNO group had higher risk of readmission (all-cause and unplanned) (HR 1.05, 95% CI: 1.00–1.10 and HR 1.06, 95% CI: 1.01–1.12) in the Crohn’s disease (CD) subgroup. Conclusion: Metabolic abnormalities were associated with an increased risk of readmission in patients with IBD, regardless of obesity.
Effect of Meteorological Factors and Air Pollutants on Daily Hospital Admissions for Ischemic Heart Disease in Lanzhou, China
Authors: Meng Xiaoxue , Jin Jianjian , Han Xia , Han Bing , Bai Ming , Zhang Zheng
Published: August 2023

Introduction: Meteorological factors and air pollutants are believed to be associated with cardiovascular disease. Ischemic heart disease (IHD) is a major public health issue worldwide. Few studies have investigated the associations among meteorological factors, air pollutants, and IHD daily hospital admissions in Lanzhou, China. Methods: We conducted a distributed lag nonlinear model on the basis of 5-year data, aiming at disentangling the impact of meteorological factors and air pollutants on IHD hospital admissions. All IHD daily hospital admissions recorded from January 1, 2015, and December 31, 2019, were obtained from three hospitals in Lanzhou, China. Daily air pollutant concentrations and meteorological data were synchronously collected from Gansu Meteorological Administration and Lanzhou Environmental Protection Administration. Stratified analyses were performed by sex and two age groups. Results: A total of 23,555 IHD hospital admissions were recorded, of which 10,477 admissions were for coronary artery disease (CAD) and 13,078 admissions were for acute coronary syndrome. Our results showed that there was a nonlinear (J-shaped) relationship between temperature and IHD hospital admissions. The number of IHD hospital admissions was positively correlated with NO2, O3, humidity, and pressure, indicating an increased risk of hospital admissions for IHD under NO2, O3, humidity, and pressure exposure. Meanwhile, both extremely low (−12°C) and high (30°C) temperatures reduced IHD hospital admissions, but the harmful effect increased with the lag time in Lanzhou, China, while the cold effect was more pronounced and long-lasting than the heat effect. Subgroup analysis demonstrated that the risk on CAD hospital admissions increased significantly in females and <65 years of age at −12°C. Conclusion: Our findings added to the growing evidence regarding the potential impact of meteorological factors and air pollutants on policymaking from the perspective of hospital management efficiency.
Validation of E/e′ Using the Index-Beat Method as an Estimate of Left Atrial Pressure in Patients with Atrial Fibrillation
Authors: Ma Gaigai , Fang Ligang , Lin Xue , Gao Peng , Fang Quan
Published: August 2023

Introduction: Echocardiographic assessment of diastolic function during atrial fibrillation (AF) remains challenging due to the irregular cardiac cycle length. We sought to assess whether the index-beat method, the beat following two preceding cardiac cycles of equal duration, could provide a more reliable measurement of E/e′ (mitral E wave/diastolic tissue Doppler velocity) than the conventional averaging of consecutive beats and hence facilitate the noninvasive estimation of elevated left atrial pressure (LAP) in patients with AF. Methods: We prospectively studied 35 patients with persistent AF who had preserved left ventricular ejection fraction and underwent radiofrequency ablation. LAP was measured in conjunction with transseptal puncture during catheter ablation. Echocardiography was performed 24 h before ablation and E/e′ was determined using the recommended averaging of 10 beats and the index-beat method, with the observers blinded to the clinical details and LAP measurements. Results: Correlation analysis showed a strong positive correlation between two methods in terms of both septal E/e′ (r = 0.841, p < 0.001) and lateral E/e′ (r = 0.930, p < 0.001). Bland-Altman analysis also showed a good agreement between the two measurement methods in terms of E/e′. E/e′ determined using both conventional averaging and the index-beat method was significantly correlated with LAP (p < 0.05). After Fisher Z transformation, we found that the index-beat septal E/e′ had a better correlation with LAP than did the conventional averaging E/e′ (r = 0.736 vs. r = 0.392, Zr = −2.110, p = 0.035). Furthermore, the index-beat method took significantly less time to measure E/e′ (mean 33.6 s; 95% confidence intervals [CIs]: 32.1 s–36.2 s) than did conventional averaging method (mean 96.2 s; 95% CI: 90.2 s–102.3 s; p < 0.001). Receiver operating characteristic curve analysis revealed that the optimal cut-off for predicting mean LAP >12 mm Hg was 11 (sensitivity 100%; specificity 77.3%) for index-beat septal E/e′ and 16 (sensitivity 61.5%; specificity 95.5%) for index-beat lateral E/e′. Conclusions: Good correlations were found between E/e′ and LAP in patients with AF, particularly with the index-beat method. Moreover, the index-beat method can easily measure E/e′ at an accuracy similar to that for the conventional averaging of consecutive beats, which can therefore be applied to assess the diastolic dysfunction and potentially improve the diagnosis of heart failure in patients with AF.
Improvement of Spinocerebellar Ataxia 3 Symptoms Treated with Eurythmy Therapy: A Case Vignette
Authors: Gerlach Katharina
Published: August 2023

A 58-year-old male with genetically confirmed spinocerebellar ataxia 3 was treated with 10 sessions of eurythmy therapy. He was rated 9 on the “Scale for Assessment and Rating of Ataxia” before therapy started. Among movement and mental symptoms, he complained about sleep disturbances, insensitivity in the feet, and spasms in the legs. The patient was asked to build strong inner images as a basis for the eurythmy therapy movement exercises. After 10 sessions, he reported improvement in sleep disturbances, insensitivity in the feet, and spasms in the legs. He improved to 7.5 points on the “Scale for Assessment and Rating of Ataxia”. In the 3 months, before starting and during eurythmy therapy, the patient did not alter the only medication taken (Bryophyllum 50% powder) and did not undergo any other therapy.
Do Disinfectant Solutions during Gargling Reach the Pharynx?
Authors: Kraus Fabian , Wech Tobias , Köstler Herbert , Hagen Rudolf , Scherzad Agmal
Published: August 2023

Introduction: In times of COVID-19, gargling disinfectant is commonly used. Disinfectant solutions seem to decrease the infection’s symptoms. For disinfection, several techniques are reported. So far, there are no data about the regions in the upper airways achieved by gargled fluid. Methods: Ten healthy volunteers without any dysphagia were investigated with a high-sensitivity flexible endoscopic evaluation of swallowing (hsFEES®) during and after gargling colored water. One volunteer repeated the gargling process in fast and real-time MRI. Results: In all cases, no color accumulation was detected on the posterior pharyngeal wall, epi- or hypopharynx during gargling. The MRI scans confirmed the results. Conclusions: hsFEES® and fast MRI provide an insight into the gargling pattern. Data show that during gargling, the fluid covers the soft tissue in the oral cavity and the anterior part of the soft palate, but not the posterior pharyngeal wall nor the epi- and hypopharynx.
Feasibility of Using the Global Tales Protocol to Elicit Personal Narratives in 10-year-Old Children in Ireland
Authors: Lyons Rena , Antonijevic-Elliott Stanislava , Barbotin Sophie , Molloy Maeve , O’Malley-Keighran Mary Pat , Spelman Jessica , Westerveld Marleen F.
Published: August 2023

Introduction: This small-scale study explored the feasibility of the Global TALES protocol in eliciting personal narratives in typically developing monolingual Irish children, using the online Zoom platform. We investigated children’s performance on measures of productivity (total number of utterances; total number of words) and syntactic complexity (MLU in words). We also documented the topics children talked about in response to the six emotion-based prompts contained in the Global TALES protocol. Methods: Nineteen typically developing children (6 male, 13 female), aged between 10.0 and 10.11 years produced personal narratives in response to the Global TALES protocol. Given COVID-19 pandemic-related public health restrictions, the language samples were elicited using Zoom. All stories were transcribed and analysed using Systematic Analysis of Language Transcripts software. Qualitative content analysis was used to code the topics of the children’s stories. Results: Sixteen participants responded to all prompts. One participant only responded to three of the six prompts. The prompt that was least successful in eliciting a response was the “problem” prompt; 15.7% (n = 3) of the children did not provide a response to this prompt. On average, children produced 40 utterances, although individual variability was high. On average, MLU was 8.7, ranging from 6 to 11. Children’s topics closely resembled those reported in the Global TALES feasibility study despite the fact, the current study took place during the COVID-19 pandemic. The most frequent topics were related to family (events, illnesses, relationships, siblings) and finding or fixing something. Conclusion: The Global TALES protocol was successful in eliciting personal narratives from 10-year-old Irish English-speaking children. Future larger scale studies are now needed to investigate if the results generalise to the wider Irish population with a view to create local benchmarks of personal narrative performance.
Interacting Networks in Social Landscapes: A Devo-Evo Approach to Socialcultural Dynamics
Authors: Jablonka Eva
Published: August 2023

Can the study of epigenetics, physiology, and cognitive science contribute to the investigation and understanding of social-cultural systems while respecting the autonomy of social research? I present a developmental system theory (DST) approach, which takes the unit of analysis to be the system of self-sustaining interactions among multiple biological, psychological, and social resources. On this view, the cybernetic architecture of the networks that constitute the system channels development so that different trajectories lead to convergent end states, accounting for the system’s developmental stability as well as shedding light on the conditions that lead to departures from typical outcomes. Based on previous work, which is extended here, I suggest that Waddington’s epigenetic landscape metaphor, which was built to illustrate the relationship between genetic networks and embryological development, is a useful tool for thinking about the temporal dynamics of social systems, capturing some important features of social stability and change at different scales and levels of social organization. I discuss five social systems using the landscape metaphor and explore the implications of this DST approach for investigating the relations between sociocultural development and evolution.
Prenatal Spina Bifida Repair: Defendable Trespassing of MOMS Criteria Results in Commendable Personalized Medicine
Authors: Moehrlen Ueli , Ochsenbein-Kölble Nicole , Stricker Sarah , Moehrlen Theres , Mazzone Luca , Krähenmann Franziska , Vonzun Ladina , Zimmermann Roland ,   Spina Bifida Study Group Zurich, Meuli Martin
Published: August 2023

Introduction: We hypothesize that after publication of the quintessence of the MOMS trial, eligibility criteria for prenatal spina bifida (SB) repair may be modified if a tenable argumentation underlies this decision. Methods: Our first 154 fetal surgery patients were analyzed with particular focus on how many, which, and why the original eligibility criteria, set forth by the MOMS Trial Protocol, were disobeyed, and what the eventually detectable, negative and positive impacts of these deviations on outcomes were. Results: A total of 152 patients (2 missing consent) were included (100%). In 69 patients (45.4%), a total of 89 eligibility criteria were disobeyed. In 54 (35.6%) cases, the following maternal criteria were concerned: gestational age at operation of >25+6 weeks in 17 (11.2%), uterine pathologies in 13 (8.6%) women, preoperative BMI ≥35 kg/m2 in 12 (7.9%), previous hysterotomy in 7 (4.6%), previous prematurity in 3 (2%), HIV/hepatitis B in 2 (1.3%), psychosocial issues in 2 (1.3%), and placenta praevia in 1 (0.7%). In 32 (21.1%) cases, fetal criteria were disobeyed 34 times: Fetal anomaly unrelated to SB in 19 (12.5%), no/minimal evidence of hindbrain herniation in 13 (8.6%), and severe kyphosis in 2 (1.3%). We could not identify cases where non-observation of criteria led to clear-cut maternal and/or fetal disadvantages. Conclusion: This study shows that MOMS trial eligibility criteria for prenatal SB repair should be modified or even abandoned with adequate medical and ethical argumentation, and with written parental informed consent after non-directive, full disclosure counseling. This clear-cut change of paradigm is a necessity as it leads toward personalized medicine, allowing more fetuses to benefit from fetal surgery than would have benefitted with the former, published, MOMS criteria in place.
The Role of Biologic Mesh and Fundoplication in the Surgical Management of Hiatal Hernias: A Multicenter Evaluation
Authors: Mohr Cassandra , Ciomperlik Hailie , Dhanani Naila , Olavarria Oscar A. , Hannon Craig , Hope William , Roth Scott , Liang Mike K. , Holihan Julie L.
Published: August 2023

Introduction: Hiatal hernia repair is associated with substantial recurrence of both hiatal hernia and symptoms of gastroesophageal reflux (GER). While small randomized controlled trials demonstrate limited differences in outcomes with use of mesh or fundoplication type, uncertainty remains. Methods: A multicenter, retrospective review of patients undergoing surgical treatment of hiatal hernias between 2015 and 2020 was performed. Patients with mesh and with suture-only repair were compared, and partial versus complete fundoplication was compared. Primary outcomes were hernia recurrence and occurrence of postoperative GER symptoms and dysphagia. Multivariable regression was performed to assess the effect of each intervention on clinical outcomes. Results: A total of 453 patients from four sites were followed for a median (IQR) of 17 (13) months. On multivariate analysis, mesh had no impact on hernia recurrence (odds ratio 0.993, 95% CI: 0.53–1.87, p = 0.982), and fundoplication type did not impact recurrence of postoperative GER symptoms (complete: odds ratio 0.607, 95% CI: 0.33–1.12, p = 0.112) or dysphagia (complete: odds ratio 1.17, 95% CI: 0.56–2.43, p = 0.677). Conclusion: During hiatal hernia repair, mesh and fundoplication type do not appear to have substantial impact on GER symptoms, dysphagia, or hernia recurrence. This multicenter study provides real-world evidence to support the findings of small RCTs.
A Prospective Randomized Controlled Pilot Study to Assess the Response and Tolerability of Cold Atmospheric Plasma for Rosacea
Authors: Hofmeyer Stella , Weber Frank , Gerds Sandra , Emmert Steffen , Thiem Alexander
Published: August 2023

Introduction: Rosacea is a common, facial, chronic inflammatory skin disease. Due to its complex pathogenesis, adequate therapy of rosacea can be challenging. An innovative recent therapeutic tool is cold atmospheric plasma (CAP), which is already established in the treatment of chronic wounds and promising in different other skin diseases. Methods: In a split-face pilot study we investigated dielectric-barrier-discharged CAP in erythemato-telangiectatic (ETR) and/or papulopustular rosacea (PPR). CAP treatment was applied on lesional skin of a randomized side once daily (90 s/area) for 6 weeks. The other untreated side served as control. Co-primary endpoints were ≥1 improvement of the Investigator Global Assessment (IGA) score on the treated side compared to control and a decline of the Dermatology Life Quality Index (DLQI) after 6 weeks. Secondary endpoints included inflammatory lesion count (papules and pustules), skin redness intensity and erythema size. Adverse events (AEs) were recorded constantly. Additionally, participants were weekly assessed for symptoms, skin condition, trigger factors, skin care, treatment success, and local tolerance parameters. All p values were calculated using the Wilcoxon signed-rank test. Results: Twelve subjects (ETR, n = 3; ETR and PPR, n = 9) completed the study. DLQI was significantly improved after 6 weeks (p = 0.007). On the CAP-treated side, lesions (p = 0.007) and erythema size (p = 0.041) were significantly reduced compared to the control. IGA (p = 0.2) and skin redness intensity (p = 0.5) did not differ significantly between control and CAP-treated side. No serious AEs occurred and treatment was well tolerated. Conclusion: CAP is a promising new treatment of rosacea, especially for PPR.
Management of Late Twin-to-Twin Transfusion Syndrome beyond 26 Weeks: Comparison between Fetoscopic Laser Therapy versus Traditional Management
Authors: Cruz-Martínez Rogelio , Gil-Pugliese Savino , Enciso-Meraz Juan Manuel , Villalobos-Gómez Rosa , López-Briones Hugo , Martínez-Rodríguez Miguel , Bermúdez-Rojas Ma. de la Luz , Medina-Jiménez Virginia , Coronel-Cruz Fausto , Pineda-Alemán Hugo , García-Espinosa Maritza , Helue-Mena Antonio , Márquez-Dávila Alejandra , Gutiérrez-Gómez Iván , Chávez-González Eréndira , Rebolledo-Fernández Carlos
Published: August 2023

Introduction: A proportion of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) can present after 26 weeks of gestation. The aim of this study was to compare perinatal outcomes of late TTTS treated by fetoscopic laser coagulation versus traditional management with amniodrainage and/or emergency preterm cesarean delivery (CD). Methods: Retrospective cohort from January 2012 to January 2023 of consecutive MCDA twin pregnancies complicated by TTTS after 26 weeks and evaluated in our referring centers. We analyzed perinatal outcomes of cases treated with fetoscopic laser surgery at our national referral fetal surgery center in Queretaro, Mexico, and compared them with those managed with traditional management (amniodrainage and/or emergency preterm CD). The primary outcome was survival at discharge and the secondary outcome was gestational age (GA) at birth. Results: Among the study population, 46 TTTS cases were treated by fetoscopy at 27+6 (26+0–31+0) weeks+days and were compared with a group of 39 cases who underwent emergency preterm CD. In comparison to the group who underwent traditional management, the group treated by laser fetoscopy showed a significantly higher GA at birth (32+3 vs. 29+1 weeks+days, p < 0.001), lower frequency of preterm delivery below 37 weeks (91.3% vs. 100%, p = 0.06), 34 weeks (63.0% vs. 100%, p < 0.001), 32 weeks (50% vs. 74.4%, p = 0.02), or 30 weeks (28.3% vs. 53.8%, p = 0.01), and significantly higher perinatal survival (89.1% vs. 71.8%, p < 0.05 of at least one twin; and 65.2% vs. 38.5%, p = 0.01 of both twins, respectively). Conclusion: MCDA twins complicated with TTTS can be treated with fetoscopic laser surgery between 26 and 31 weeks of gestation, which is a feasible and safe option, and such cases are associated with a higher GA at birth and better perinatal survival than those managed with amniodrainage and/or emergency preterm CD.
Large Chromosome 2p Duplication-Associated Mechanisms and Clinical Presentations
Authors: Fang Xiaolan , Hilton Benjamin , Clarkson Katie , Rogers R. Curtis , Schroer Richard , Childers Anna , Patterson Wesley G. , Davis Jessica M. , Everman David B. , DuPont Barbara R.
Published: August 2023

Chromosome 2p (chr2p) duplication, also known as trisomy 2p, is a rare chromosome abnormality associated with developmental delay, intellectual disability, behavioral problems, and distinctive facial features. Most of the reported cases involving trisomy 2p include additional copy number variants (CNVs) in other regions of the genome and are usually small in size. Little is known about the clinical outcomes of large duplications of chr2p as the sole cytogenetic abnormality. In this study, 193 samples at the Greenwood Genetic Center (GGC) with CNVs involving chr2p were evaluated, out of which 86 had chr2p duplications. Among them, 8 patients were identified with large chr2p duplications ranging in size from 9.3 Mb to 89 Mb, and no deletions or duplications involving other chromosomes were identified in those patients. These duplications were associated with inverted duplication, tandem duplication, and duplication as the result of translocation, with no additional CNVs identified by microarray analysis. Confirmation by conventional cytogenetics was performed in 7 of the 8 patients, and the translocations were confirmed by fluorescence in situ hybridization. Interestingly, 1 patient was found to have mosaic complete trisomy 2p as the result of an unbalanced de novo (X;2) chromosomal translocation. X-inactivation was skewed toward the derivative X chromosome, yet it did not appear to extend into the chromosome 2 material. Various shared clinical manifestations were observed in the individuals in this study, including developmental delay, hemifacial hypoplasia, cleft palate, and short stature, and they also have distinct features such as hypotonia, cerebellar hypogenesis, and corpus callosum agenesis, which might result from a gene dosage effect of the duplication. In conclusion, single-event large chr2p duplications can result from different mechanisms, including inverted or tandem duplications within chromosome 2, or translocations involving chromosome 2 and other chromosomes. Partial or complete trisomy 2p is commonly associated with developmental delay, and additional clinical features may be related to gene dosage effects.
Immediate and Sustained Root Caries Prevention of Fluoride Varnish Combined with Toothpastes
Authors: Zamperini Camila A. , Bedran-Russo Ana K.
Published: August 2023

The aim of this study was to determine the immediate and sustained effect of a fluoride varnish and its combinations with toothpastes in preventing root caries development using a salivary microcosm in vitro model. Human root dentin specimens (n = 150) were randomly divided into 5 experimental protocols (n = 30): (1) Fluoride Varnish (V); (2) V followed by Paste One (V + PO); (3) V followed by Paste Plus (V + PP); (4) V followed by PO and PP (V + PO + PP); and (5) No treatment (control). One varnish layer was applied on the specimens (except for the control group) and kept for 18 h. Then, the varnish was removed and toothpaste treatments were initiated according to experimental groups. For the short-term incubation model (n = 15), the specimens were also immediately subjected to 7-day cariogenic challenge. For that, human saliva was used as bacterial inoculum and McBain artificial saliva containing 2% sucrose as growth medium. The other half of the specimens (n = 15) were used to study the varnish’s sustained effect by long-term incubation (8 weeks) before cariogenic challenge. The protocols’ anti-caries properties were evaluated by dentin porosity (rhodamine intensity; RI) and mineral density, while their anti-biofilm effects were evaluated using biofilm’s biomass and viability assays. For short- and long-term incubation models, all experimental regimens resulted in statistically significant decreases (p < 0.05) in the RI (up to 180 μm and 120 μm, respectively) as well as higher mineral density compared to No treatment (p < 0.001). V + PO + PP and/or V + PO resulted in statistically lower RI compared to V for some depths (p < 0.05) in both models. There were changes in RI and mineral density within groups over time. All experimental treatments exhibited anti-biofilm effects. All prevention protocols exhibited immediate and sustained anti-caries effect against root caries development. The combination of a fluoride varnish with PO resulted in superior additional anti-caries effects.
Simultaneous EYFP-CENH3/H2B-DsRed Expression Is Impaired Differentially in Meristematic and Differentiated Nuclei of Arabidopsis Double Transformants
Authors: Schubert Veit , Weißleder Andrea , Lermontova Inna
Published: August 2023

Fluorescence live-cell microscopy is important in cell biology to perform artifact-free investigations. To analyze the dynamics of chromatin and centromeres at different stages of the cell cycle in nuclei and chromosomes, we performed simultaneous EYFP-CENH3/H2B-DsRed and single H2B-YFP transformations in Arabidopsis wild-type and cohesin T-DNA mutants. All constructs were under the control of the strong CaMV 35S promoter. While a strong silencing of fluorescence expression occurred differently in leaf and root tissues in the double transformants, nearly all single-transformed wild-type and most mutant cells showed H2B-YFP fluorescence. It seems that for an efficient co-expression of two fluorescence proteins, endogenous promoters and terminators should be used.
Genetic Testing and Other Healthcare Use by Black and White Individuals in a Genomic Sequencing Study
Authors: Saylor Katherine W. , Klein William M.P. , Calancie Larissa , Lewis Katie L. , Biesecker Leslie G. , Turbitt Erin , Roberts Megan C.
Published: August 2023

Introduction: Early adopters play a critical role in the diffusion of medical innovations by spreading awareness, increasing acceptability, and driving demand. Understanding the role of race in the context of other characteristics of potential early adopters can shed light on disparities seen in the early implementation of genomic medicine. We aimed to understand the association between self-identified race and individual experience with genetic testing outside of the research context. Methods: We assessed factors associated with the odds of having ever received genetic testing prior to enrollment in a genomic sequencing study among 674 self-identified white and 407 self-identified African, African American, or Afro-Caribbean (“Black”) individuals. Results: Controlling for individual determinants of healthcare use (demographics, personality traits, knowledge and attitudes, and health status), identifying as Black was associated with lower odds of prior genetic testing (OR = 0.43, 95% CI [0.27–0.68], p < 0.001). In contrast, self-identified race was not associated with the use of non-genetic clinical screening tests (e.g., echocardiogram, colonoscopy). Black and white individuals were similar on self-reported personality traits tied to early adoption but differed by sociodemographic and resource facilitators of early adoption. Conclusion: Persistent racial disparities among early adopters may represent especially-entrenched disparities in access to and knowledge of genomic technologies in clinical settings.