bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of female and male patients suffering from coronary artery disease
Authors: Jäckel Markus , Kaier Klaus , Rilinger Jonathan , Wolf Dennis , Peikert Alexander , Roth Katrin , Oettinger Vera , Dawid Leander Staudacher , Zehender Manfred , Bode Christoph , Constantin Von Zur Mühlen , Stachon Peter
Published: September 2021

Presentation and mortality of coronary artery disease (CAD) substantially differs in both sexes. Most of the existing data analyzing sex differences is older than 10 years and mostly was retrieved in clinical trials, which are potentially structured with a bias against the inclusion of women, leading to a potential selection-bias. Meanwhile, with better diagnostic and therapeutic options, actual data analyzing sex differences in emergency CAD patients is rare.

Data on all emergency case numbers with CAD diagnosis in Germany 2017 was retrieved from the German Institute for Medical Documentation and Information. DRG, OPS, and ICD codes were used to determine comorbidities, in-hospital course, and outcome. Competing risk regression analysis for in-hospital mortality was performed analyzing age, European System for Cardiac Operative Risk Evaluation (EuroSCORE), severity of CAD, clinical presentation type and sex.

264,742 patients were included. Female patients were older and had more comorbidities. Three-vessel CAD was significantly less present in female patients (36.5% vs 47.5%; P < .001). After adjusting for age, EuroSCORE and severity of CAD, female sex was an independent predictor of lower in-hospital mortality (subdistribution hazard ratio [sHR] 0.94, 95% CI: 0.90–0.98, P = .002) in the whole cohort and in non-ST-segment elevation myocardial infarction (NSTEMI) patients (sHR 0.85, 95% CI: 0.79–0.92, P < .001), whereas in ST-segment elevation myocardial infarction (STEMI) patients, female sex was associated with a higher in-hospital mortality (sHR 1.07, 95% CI: 1.01–1.14, P = .029).

In all patients admitted as emergency with CAD diagnosis and in all NSTEMI patients, female sex is protective, whereas in STEMI patients, females show a higher in-hospital mortality risk.
The natural trends of C-reactive protein after hip arthroplasty for femoral neck fracture without infection
Authors: Cho Myung-Rae , Choi Won-Kee , Jun Chung-Mu , Song Suk-Kyoon
Published: September 2021

The aim of this study was to estimate the degree of normalization of C-reactive protein (CRP) at 2-weeks and 4-weeks after hip arthroplasty after femoral neck fracture. We also wished to determine whether the degree of CRP normalization differs after total hip arthroplasty (THA) compared to bipolar hemiarthroplasty (BH). We also wanted to analyze the patient factors that may influence CRP normalization.

We conducted a retrospective study of 135 patients who had undergone THA (32 cases) or BH (103 cases) for femoral neck fracture by single surgeon from January 2015 to December 2019. We analyzed CRP levels during the preoperative period, the early postoperative period, the 2-week postoperative period, and the 4-week postoperative period.

In THA, CRP was normalized in 4 patients (12.5%) and in 15 patients (46.9%) within 2-weeks and 4-weeks after surgery, respectively. In BH, CRP was normalized in 16 patients (15.5%) and in 52 patients (50.5%) within 2-weeks and 4-weeks after surgery, respectively. There were no statistical differences between THA and BH. Compared to women, men were 3.78 (95% confidence interval, 1.05–13.63) times less likely to have normalized CRP at 2-weeks after surgery (P = .042). Compared to women, men were 3.01 (95% confidence interval, 1.44–6.27) times less likely to have normalized CRP at 4-weeks after surgery (P = .003).

Only 50% of patient's CRP level was normalized during 4-week postoperative period. In men, CRP levels were significantly higher than women in whole period. In the case of THA, the CRP level was higher only in early postoperative period compared to BH, and there was no difference since then.
Association between early menarche and suicidal behaviors in Korean girl adolescents
Authors: Kim Soo Rim , Lee Sujin , Chung Jae Ho
Published: September 2021

Early menarche can be the socio-psychological problems. We studied the association between early menarche and suicidal risk behaviors among South Korean girl adolescents using national-wide data.

Web-based self-report data from 2006 to 2015 the Korea Youth Risk Behavior Web-based Survey data were used in this study. Menarche status was divided into an “early menarche” group (at <12 years of age) versus “not early” menarche group (at ≥12 years of age).

Participants with adolescent girls with early menarche group showed a higher prevalence of substance use, higher levels of stress, poorer self-rated health status, unhappier perceiveness, more frequent depressed mood, inter-sexual kissing or petting, inter-sexual intercourse, homosexual kissing or petting, being the victim or the assailant of sexual assaults, sexual transmitted diseases experience, pregnancy, and abortion experience than the not early menarche group. Adolescent girls with early menarche who had suicidal ideation (25.4% vs 22.2%, P < .001), suicidal plans (4.1% vs 2.6%, P < .001), and suicidal attempts (6.8% vs 5.2%, P < .001) were higher than that in the adolescent girls with not early menarche. A multivariate analysis after adjusting revealed that the odds ratios for suicidal ideation, plans, and attempts were 1.07 (95% confidence interval [CI]: 1.05–1.10), 1.35 (95% CI: 1.28–1.41), and 1.13 (95% CI: 1.09–1.18), respectively.

Adolescent girl with early menarche was associated with suicidal behaviors.
The relationship between smartphone use and dry eye disease
Authors: Al-Marri Khaloud , Al-Qashoti Maha , Al-Zoqari Hissa , Elshaikh Usra , Naqadan Alya , Saeed Raghad , Faraj Jameela , Shraim Mujahed
Published: September 2021

Background:

Emerging research findings suggest a potential relationship between smartphone use (SPU) and dry eye disease (DED), which has not been systematically reviewed.

Objectives:

The aim of this study was to systematically review and synthesize evidence on the relationship between SPU and DED.

Methods:

A systematic search of Medline, EMBASE, CINAHL, and PsychINFO bibliographic databases from their inception to January 15, 2021. Study screening, full-text assessment, study selection and exclusion, data extraction, and quality assessment was performed independently by at least two review authors.

Results:

Four studies were included in the review (3 cross-sectional studies and 1 nonrandomized clinical trial). A narrative synthesis of findings was used due to heterogeneity among study designs and measures of association summarizing the relationship between SPU and DED. All included studies were conducted in South Korea and included school children, college students, or young adults. Three of the 4 included studies showed an association between SPU and DED.

Conclusions:

There is some evidence that SPU is associated with DED. However, this evidence is limited by a small number of studies of satisfactory methodological quality. There is a great need for high-quality studies to further investigate the relationship between SPU and DED and identify mechanisms underlying this potential relationship. This information is important for raising public awareness about the negative effect of SPU on eye health and development of clinical guidelines for this potentially emerging SPU-driven eye condition.
Treatment of tibial plateau fractures involving the posterolateral column using the extended anterolateral approach
Authors: Mao Wenwen , Chen Gang , Zhu Yousen , Zhang Min , Ru Jiangying , Wang Jinguang , Li Li
Published: September 2021

To summarize the surgical technique and clinical effects of the extended anterolateral approach for the treatment of Schatzker type II and Schatzker type V/VI involving the posterolateral column tibial plateau.

From January 2015 through December 2018, 28 patients with tibial plateau fractures involving the posterolateral column were included in the study. Among them, 16 patients were Schatzker type II treated using an extended anterolateral approach with lateral tibial locking compression plate fixation. Twelve patients were Schatzker type V or VI treated using an extended anterolateral combined with a medial approach using lateral tibial locking compression plate plus medial locking compression plate fixation. All cases were followed up for 15 to 31 months, with an average follow-up of 22.5 ± 3.7 months. During the follow-up, the tibial plateau angle (TPA), lateral posterior angle (PA) and Rasmussen radiological criteria were used to evaluate the effect of fracture reduction and fixation; the Hospital for Special Knee Surgery score and the range of motion were used to evaluate knee function. Additionally, the Lachman and knee Valgus (Varus) stress tests were used to evaluate anteroposterior and lateral stability of the knee.

All fractures healed. At the 12-month follow-up, the Schatzker type II group revealed a mean TPA of 86.38 ± 3.92°, a mean PA of 7.43 ± 2.68°, and a mean Rasmussen radiological score of 16.00 ± 2.06 points. The Schatzker type V/VI group showed a mean TPA of 84.91 ± 3.51°, a mean PA of 9.68 ± 4.01°, and a mean Rasmussen radiological score of 15.33 ± 2.99 points. During the 1-year follow-up, when the postoperative PA was re-measured, the TPA and Rasmussen score of the 2 groups did not change significantly (P > .05). At the last follow-up, the Schatzker type II group showed a knee flexion angle of 110° to 135° and a mean HHS score of 88.37 ± 10.01 points. The Schatzker type V/VI group revealed a knee flexion angle of 100° to 130° and a mean HHS score of 82.17 ± 10.76 points. Additionally, up to the last follow-up, the Lachman and knee Valgus (Varus) stress test results of the 2 groups were negative. No complications were found.

The extended anterolateral approach is a good choice to treat tibial plateau fractures involving the posterolateral column.
Stroke-associated pneumonia
Authors: Chen Yuanyuan , Yang Hongyan , Wei Hui , Chen Yanqin , Lan Meijuan
Published: September 2021

Stroke-associated pneumonia (SAP) is a spectrum of pulmonary infections in patients within 7 days of stroke. Which is one of the most common complications after stroke and is significantly associated with a poor prognosis of stroke. To the best of our knowledge, a bibliometric method was not previously used to analyze the topic of SAP; we aim to describe the situation and evolution of SAP from 2003 to 2020, and to discuss the research hotspots and frontiers.

A total of 151 articles were retrieved from the Scopus database. Bibliometric analysis was used to explore the dynamic trends of articles and the top subject areas, journals, institutes, citations, and co-keywords. VOS viewer software (version 1.6.15) was used to graphically map the hot topics of SAP based on the co-keywords.

A total of 151 articles were identified. Articles have increased over the recent years and faster in the last 2 years (55 articles, 36.4%), the majority of subject areas are medicine (124 articles, 82.1%) and neuroscience (38 articles, 25.2%). The “Journal Of Stroke And Cerebrovascular Diseases” with 15 articles has been scored as the first rank followed by “Plos One.” Regarding the geographical distribution of articles, China is the most productive country with 50 articles (33.1%), others are more prominent in Europe, and most institutes are universities. Citations have increased over time, the main country of the top five highly cited published articles are Germany and before 2008. The co-keywords are mainly divided into four aspects: risk factors, predictive scores, preventions, and outcomes.

This study could provide practical sources for researchers to find the top subject areas, journals, institutes, citations, and co-keywords. Moreover, the study could pave the way for researchers to be engaged in studies potentially lead to more articles in this field.
Real-world efficacy and safety of switching to bictegravir/emtricitabine/tenofovir alafenamide in older people living with HIV
Authors: Rolle Charlotte-Paige , Nguyen Vu , Patel Kiran , Cruz Dan , DeJesus Edwin , Hinestrosa Federico
Published: September 2021

Approximately 50% of people living with HIV (PLWH) in the United States are ≥50 years old. Clinical trials of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) demonstrated potent efficacy and favorable safety in older PLWH; however, real-world data would be useful to validate these results.

Retrospective cohort study.

We evaluated records from PLWH aged ≥50 years at the Orlando Immunology Center who were switched to B/F/TAF between February 2018 and August 2019. Eligible patients had baseline HIV-1 RNA <50 copies/mL and 48 weeks of follow-up data. The primary endpoint was maintenance of HIV-1 RNA <50 copies/mL at Week 48. The impact of switching to B/F/TAF on drug–drug interactions (DDIs) and safety parameters were also assessed.

Three-hundred and fifty patients met inclusion criteria, median age was 57 years, 20% were women, and 43% were non-White. Fifty-five percent of patients switched from integrase inhibitor-based regimens; the most common reason for switch was simplification. At Week 48, 330 (94%) patients maintained an HIV-1 RNA <50 copies/mL and 20 (6%) had an HIV-1 RNA between 50 and 400 copies/mL. One-hundred and forty potential DDIs were identified in 121 (35%) patients taking a boosting agent or rilpivirine at baseline that were resolved after switching to B/F/TAF. Treatment-related adverse events occurred in 51 (15%) patients (all Grade 1–2) and led to 8 discontinuations.

In this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH.
General anesthesia with cisatracurium and sevoflurane for a patient with primary carnitine deficiency receiving L-carnitine therapy
Authors: Ai Ling , Fang Yan
Published: September 2021

Rationale:

Lipid storage myopathies (LSMs) are a series of genetic disorders of lipid metabolism predominantly affecting muscle. The low incidence and lethal properties of this disease make anesthesia experience limited in such patients. Among all etiologies of LSMs, primary carnitine deficiency (PCD) is now considered highly treatable by early administration of L-carnitine, though it remains unclear whether L-carnitine is effective enough to protect diseased muscle against conventionally used neuromuscular blocking agents (NMBAs) during general anesthesia. Currently, no data are available concerning possible prolonged muscle weakness in these cases.

Patient concerns:

This case presents a 43-year-old female who was diagnosed with a PCD-induced LSM 3 years ago due to fatigability and exertional myalgias and has been treated with L-carnitine ever since. At the time of this report, she was admitted for uterine fibroids and scheduled for selective open gynecologic surgery under general anesthesia.

Diagnosis:

The patient's diagnosis of PCD-induced LSM was based on the clinical features, muscle biopsy, and diminished organic cation/carnitine transporter 2 (OCTN2) transporter activity in the patient's skin fibroblasts.

Interventions:

L-carnitine was taken by the patient until the morning of surgery. General anesthesia with cisatracurium and sevoflurane was selected as the anesthetic plan during the operation. The train-of-four (TOF) test was adopted as additional monitoring, particularly to track the recovery of neuromuscular function.

Outcomes:

The patient was extubated successfully following a spontaneously restored TOF ratio (TOFR) of 0.9. Nonetheless, we recorded a prolonged efficacy of cisatracurium in the clinical duration and the recovery time with TOFRs of 0.7 and 0.9, respectively.

Lessons:

The conventional dose of cisatracurium combined with a low dose of sevoflurane can be safely used in patients with LSMs without additional anesthetic risks. Meanwhile, continuous TOF monitoring is recommended to perform high-quality anesthesia.
The influence of edema on the bisoprolol blood concentration after bisoprolol dermal patch application
Authors: Takahashi Yuji , Sonoo Tomohiro , Nakano Hidehiko , Naraba Hiromu , Hashimoto Hideki , Nakamura Kensuke
Published: September 2021

Background:

Beta-blocking is important for critically ill patients. Although some patients are required to continue taking beta-blockers after they no longer need critical care, some of these patients have impaired swallowing abilities. Bisoprolol dermal patches have recently been introduced and appear to be a good alternative to oral bisoprolol tablets. However, it is still unclear whether the pharmacodynamics of such patches are affected by edema in patients who have experienced critical care. This study aimed to clarify the effects of systemic edema on beta-blocker absorption from dermal patches in critically ill patients.

Method:

Patients who exhibited tachycardia and impaired swallowing function after critical care were included in this study. They were assigned to either the edema group (n = 6) or no edema group (n = 6) depending on the presence/absence of edema in the lower extremities. A bisoprolol dermal patch was pasted onto each subject, and the blood bisoprolol concentration was checked at 8 timepoints over the next 24 hours. The area under the serum concentration time curve, maximum concentration observed (Cmax), and time of maximum concentration observed were also examined.

Result:

The mean blood bisoprolol concentrations of the 2 groups were not significantly different at 2, 4, 6, 8, 10, 12, 16, or 24 hours after the patch application. The area under the serum concentration time curve and maximum concentration observed were not different between the groups. The mean heart rates of the 2 groups were not significantly different at 6, 12, or 24 hours after the patch application (Student t test, P = .0588, P = .1080, and P = .2322, respectively).

Conclusion:

In this study, the blood concentration of bisoprolol and its heart rate-reducing effects after bisoprolol dermal patch application might not be affected by systemic edema in the lower extremities.
Lesion detection in 18F-sodium fluoride bone imaging: a comparison of attenuation-corrected versus nonattenuation-corrected PET reconstructions from modern PET-CT systems
Authors: Bebbington Natalie Anne , Zacho Helle Damgaard , Holdgaard Paw Christian
Published: September 2021

Objectives

An earlier study demonstrated comparable lesion detection between attenuation-corrected (AC) and nonattenuation-corrected (NAC) 18F-sodium fluoride (NaF) PET images, which is relevant for computed tomography (CT) radiation dose-saving. However, this finding may not be applicable to newer systems. The aim was to compare lesion detection between AC and NAC NaF PET images on modern PET-CT systems.

Methods

One expert and one nonexpert observer retrospectively surveyed NaF PET data in 25 breast cancer patients. At both lesion and patient level, each observer classified bone abnormalities as malignant, equivocal or benign, from NAC and AC PET images in the absence of CT. Expert interpretation of NaF PET-CT with the review of all diagnostic imaging/pathology reports for at least the subsequent 12 months provided reference standard metastases status at the patient level. Two-tailed Wilcoxon signed-rank tests measured statistically significant differences in total lesion detection between AC and NAC PET. Quadratic-weighted kappa score measured agreement in patient metastases status between observers.

Results

On a lesion-basis, AC PET images showed significantly more lesions than NAC for both the expert (122 versus 96; P = 0.002) and nonexpert (146 versus 132; P = 0.036) observers, with a large number of patients demonstrating disparity between AC and NAC images. For metastases status at the patient level without CT, NAC PET showed slightly better diagnostic accuracy than AC due to fewer false-positive results, as fewer lesions were identified.

Conclusion

AC PET data provided superior lesion detection to NAC in NaF bone examinations and are thus required for clinical interpretation.
Birth Satisfaction During the Early Months of the COVID-19 Pandemic in the United States
Authors: Mollard Elizabeth , Kupzyk Kevin
Published: September 2021

Purpose:

The purpose of this study was to describe birth satisfaction in women who gave birth in U.S. hospitals during the earliest months of the COVID-19 pandemic (March–July 2020).

Study Design and Methods:

A cross-sectional survey of 747 postpartum women who gave birth in the United States during the early COVID-19 pandemic was conducted. Participants in the United were recruited via social media. They completed a questionnaire that included demographic, health, and obstetric experience questions, and the Birth Satisfaction Scale-Revised. Descriptive statistics, t-tests, analysis of variance (ANOVA) models, and nonparametric correlations were performed.

Results:

Higher birth satisfaction scores were associated with higher income, marriage, white race, vaginal birth, having a birth partner present, and sufficient support during birth. Factors negatively associated with birth satisfaction were separation from infant, unplanned cesarean birth, neonatal intensive care unit admission, hypertension, preeclampsia, hemorrhage, depression, and anxiety.

Clinical Implications:

Presence of birth partners, sufficient birth support, and minimizing separation of mother and infant improve birth satisfaction. Obstetric complications, including unplanned cesarean birth, negatively affect birth satisfaction. There are racial disparities in birth satisfaction. It is critical to develop further interventions to end racism in maternal health care.
Facilitators and Barriers to Critical Service-Learning Goals in a Community-Academic Relationship
Authors: Mayer Kala A.
Published: September 2021

Background:

Educational exposure to authentic relationships where power is distributed is needed to prepare nursing students as social justice and patient-centered care practitioners and advocates.

Purpose:

The purpose of this study was to identify, describe, and understand facilitators and barriers to critical service-learning (SL) goals in an existing community-academic SL relationship.

Methods:

Community partners were surveyed. Findings were compared with known factors in the literature that can facilitate or inhibit a relationship's success.

Results:

Identification and description of SL relationship facilitators and barriers included partner-reported benefits from involvement in SL and limited satisfaction with their role in designing SL curriculum.

Conclusions:

Recommendations, such as increasing opportunities for partner involvement, provide insight into how to work toward critical SL goals in existing relationships. The equitable involvement of partners in nursing education processes has benefits for both students and community organizations.
Relationships Among Exercise, Mindfulness, Mental Health, and Academic Achievement Among Prelicensure Nursing Students
Authors: Niedermeier Josie , Mumba Mercy Ngosa , Barron Keri , Andrabi Mudasir , Martin Rebecca , McDiarmid Alex
Published: September 2021

Background:

Nursing school is challenging and can be stressful for many students. Nursing students are also susceptible to stress, anxiety, and depression. Exercise and mindfulness-based interventions (MBIs) have been shown to improve mental health outcomes in other populations, but it is not known how these strategies influence academic achievement.

Purpose:

The purpose of this study was to examine the relationships among exercise, mindfulness, academic achievement, and mental health among undergraduate nursing students.

Methods:

This study used a cross-sectional design that uses correlational, regression, and mediation analyses.

Results:

Mindfulness was inversely associated with depression and anxiety and, although not statistically significant, was positively associated with academic achievement. Exercise was not significantly associated with anxiety or academic achievement but was associated with depression.

Conclusions:

Evidence-based interventions that promote mindfulness among nursing students should be implemented to promote mental health and academic achievement, especially because MBIs are cost-effective and convenient alternatives to other psychotherapies.
Application of the Improving Pediatric Sepsis Outcomes Definition for Pediatric Sepsis to Nationally Representative Emergency Department Data
Authors: Ramgopal Sriram , Adler Mark D. , Horvat Christopher M.
Published: September 2021

Introduction:

To compare encounter estimates and demographics of pediatric patients (<18 years) meeting modified Improving Pediatric Sepsis Outcomes (IPSO) criteria for sepsis to cohorts obtained using other criteria for pediatric sepsis from administrative datasets.

Methods:

We analyzed data from the National Hospital Ambulatory Medical Care Survey for 2003–2018. We report encounter estimates, demographics, and treatments among pediatric sepsis events using 3 criteria: modified IPSO criteria for sepsis, explicit criteria using diagnostic codes, and implicit severe sepsis criteria requiring the presence of infection and organ dysfunction.

Results:

The modified IPSO, explicit, and severe sepsis criteria estimated the yearly encounter rates as 116,200, 27,900, and 56,000 respectively. The modified IPSO sepsis criteria accounted for 0.4% of emergency department encounters, with a high proportion of patients who received antibiotics (99.2%, 95% CI 97.8%–100.0%), intravenous fluids (100.0%, 95% CI 99.9%–100.0%), and blood cultures (98.7%, 95% CI 96.9%–100.0%). The explicit cohort had lower proportions with blood cultures (60.6%, 95% CI 40.4%–80.7%) and antibiotic use (77.0%, 95% CI 63.1%–90.8%), but a high proportion admitted (84.0% 95% CI 73.4%–95.7%). The severe sepsis definition had low proportions with blood cultures (12.7%, 95% CI 6.3%–19.1%) and admission (21.1%, 95% CI 14.5%–27.8%).

Conclusions:

Pediatric sepsis estimates differed based on the criteria used for cohort ascertainment. The modified IPSO sepsis criteria group had higher acuity than the severe sepsis cohort but lower acuity than the cohort identified using the explicit sepsis criteria.
Comparison of mineral and hazardous heavy metal contents in
Lentinula edodes produced from Korea and
China
Authors: Jeong Hee-Gyeong , Kim Kyung-Je , Seo Kyoung-Sun , Jin Seong-Woo , Koh Young-Woo , Im Seung-Bin , Ha Neul-I , Kim Jung-Beom
Published: September 2021

Lentinula edodes, an edible mushroom, is mainly produced in
Korea, China, and Southeast Asia. Thus, very few studies have reported the
identification of the country origin of L.
edodes samples. Herein, the macro mineral, trace mineral,
and hazardous heavy metal contents of domestic and Chinese L.
edodes samples were analyzed and their production countries
were compared. The mineral contents of 13 domestic and 17 Chinese L.
edodes samples were analyzed using atomic absorption
spectrophotometer and inductively coupled plasma mass spectrometer. The Na, Mg,
K, and Ca contents in domestic L. edodes were determined to be
161.33, 746.22, 17,676.84, and 50.50 mg/kg, respectively, whereas those in
Chinese L. edodes were 310.69, 318.49, 11,182.01, and 33.36
mg/kg, respectively. The Cr and Cu contents in domestic and Chinese L.
edodes were 2.82 and 77.13 mg/kg (Cr) and 12.955 and 101.19 mg/kg
(Cu), respectively. The hazardous heavy metal contents in domestic and Chinese
L. edodes were determined to be within the levels
recommended by the Korean Food Code. Taken together, our results reveal
significant differences between Na, Mg, and K contents (p<0.001) and Cr
content (p<0.01) in domestic and Chinese L. edodes
samples. Thus, Na, Mg, K, and Cr contents may serve as basic data to determine
the origin of domestic and Chinese L. edodes samples; further
studies on the Na, Mg, K, and Cr contents in domestic and Chinese L.
edodes samples are needed for identifying the country origin of
this mushroom.
Covid-19 in the Phase 3 Trial of mRNA-1273 During the Delta-variant Surge
Authors: Baden Lindsey R. , El Sahly Hana M. , Essink Brandon , Follmann Dean , Neuzil Kathleen M. , August Allison , Clouting Heather , Fortier Gabrielle , Deng Weiping , Han Shu , Zhao Xiaoping , Leav Brett , Talarico Carla , Girard Bethany , Paila Yamuna D. , Tomassini Joanne E. , Schödel Florian , Pajon Rolando , Zhou Honghong , Das Rituparna , Miller Jacqueline
Published: September 2021

Background

Following emergency use authorization in December 2020, the Coronavirus Efficacy (COVE) trial was amended to an open-label phase, where participants were unblinded and those randomized to placebo were offered vaccination. Emergence of the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with increased incidences of coronavirus disease 2019 (Covid-19) among unvaccinated and vaccinated persons. This exploratory analysis evaluated the incidence and genetic sequences of Covid-19 cases in the ongoing COVE trial during the open-label phase, with a focus on July-August 2021, when delta-variants surged in the US.

Methods

Covid-19 cases were identified in participants initially randomized to mRNA-1273 (vaccinated from July-December 2020) and those initially randomized to the placebo (vaccinated December 2020-April 2021) who received at least one dose and were SARS-CoV-2-negative at baseline in the modified-intent-to-treat population were analyzed. Included were Covid-19 cases occurring after 26-Mar-2021 with positive RT-PCR results in nasopharyngeal samples (central lab test) and reported Covid-19 symptoms. Genetic sequencing of Covid-19 cases was also performed.

Results

There were 14,746 participants in the earlier mRNA-1273 (mRNA-1273e) group and 11,431 in the later placebo-mRNA1273 (mRNA-1273p) group. Covid-19 cases increased from the start of the open-label phase to July-August 2021. During July and August, 162 Covid-19 cases occurred in the mRNA-1273e group and 88 in the mRNA-1273p group. Of the cases sequenced, 144/149 [97%]) in the mRNA-1273 and 86/88 (99%) in the mRNA-1273p groups were attributed to delta. The incidence rate of Covid-19 was lower for the mRNA-1273p (49.0/1000 person-years) versus mRNA-1273e (77.1/1000 person-years) group [36.4% (95% CI 17.1%-51.5%) reduction]. There were fewer severe Covid-19 cases in the mRNA-1273p (6; 6.2/1000 person-years) than mRNA-1273e (13; 3.3/1000 person-years) [46.0% (95% CI −52.4%-83.2%) reduction]. Three Covid-19 related hospitalizations occurred with two resulting deaths in the mRNA-1273e group.

Conclusion

Incidence rates of Covid-19 and severe Covid-19 were lower during the months when delta was the dominant variant (July/August 2021) among COVE participants vaccinated more recently. Analysis of COVID-19 cases from the open-label phase of the COVE study is ongoing.
Narcolepsy with cataplexy is caused by epigenetic silencing of hypocretin neurons
Authors: Seifinejad Ali , Neiteler Almar , Li Sha , Pfister Corinne , Fronczek Rolf , Shan Ling , Garrett-Sinha Lee A. , Frieser David , Honda Makoto , Arribat Yoan , Grepper Dogan , Amati Francesca , Picot Marie , Iseli Christian , Chartrel Nicolas , Lammers Gert J. , Liblau Roland , Vassalli Anne , Tafti Mehdi
Published: September 2021

Narcolepsy with cataplexy is a chronic sleep disorder characterized by hypocretin deficiency. The condition is believed to result from autoimmune destruction of hypocretin (HCRT) neurons, although direct evidence is lacking and mere Hcrt gene inactivation causes full-blown narcolepsy in mice. Here we show that the expression of another hypothalamic neuropeptide, QRFP, is lost in mouse models with HCRT cell-ablation, but tends to be even increased in Hcrt gene knockout mice, suggesting that QRFP expression can be used as a proxy for the presence or absence of HCRT neurons. Similar to Hcrt knockout mice, narcolepsy patients show intact hypothalamic QRFP expression, and cerebrospinal fluid levels of QRFP peptide are increased, suggesting their HCRT neurons are intact. We show that the human HCRT gene promoter is methylation-sensitive in vitro, and is hypermethylated in the hypothalamus of patients selectively at a putative PAX5:ETS1 binding site within the proximal HCRT promoter. Ets1-KO mice display downregulated Hcrt expression, while pax5-ets1 knockdown in zebrafish causes decreased hcrt expression, decreased activity and sleep fragmentation, similar to narcolepsy patients. Our results suggest that HCRT neurons are alive, but epigenetically silenced, in the hypothalamus of narcolepsy patients, opening the possibility to reverse or cure narcolepsy.
Effects of memantine and high dose vitamin D on gait in the APP/PS1 mouse model of Alzheimer’s disease following vitamin D deprivation
Authors: Broberg Dana , Wong Dickson , Bellyou Miranda , Montero-Odasso Manuel , Beauchet Olivier , Annweiler Cedric , Bartha Robert
Published: September 2021

Background

Altered gait is a frequent feature of Alzheimer’s disease (AD), as is vitamin D deficiency. Treatment with memantine and vitamin D can protect cortical axons from exposure to amyloid-β and glutamate toxicity, suggesting this combination may mitigate altered gait in AD.

Objective

Investigate the effects of vitamin D deprivation and subsequent treatment with memantine and vitamin D enrichment on gait performance in APPswe/PS1dE9 mice.

Methods

Male APPswe/PS1dE9 mice were split into four groups (n=14 each) at 2.5 months of age. A control group was fed a standard diet throughout while the other three groups started a vitamin D-deficient diet at month 6. The VitD− group remained on this deficient diet for the rest of the study. At month 9, the remaining two groups began treatment with either memantine alone or memantine combined with 10 IU/g of vitamin D. Gait performance was assessed at months 6, 9, 12, and 15.

Results

Vitamin D deprivation led to a 13% increase in hind stride width by month 15 (p<0.001). Examination of the treatment groups at month 15 revealed that mice treated with memantine alone still showed an increase in hind stride width compared to controls (p<0.01), while mice treated with memantine and vitamin D did not (p=0.21).

Conclusion

Vitamin D deprivation led to impaired postural control in the APPswe/PS1dE9 model. Treatment with memantine and vitamin D, but not memantine alone, prevented this impairment. Future work should explore the potential for treatments incorporating vitamin D supplementation to improve gait in people with AD.
GBRAP: a tool to retrieve, parse and analyze GenBank files of viral and bacterial species
Authors: Vischioni Chiara , Giaccone Valerio , Catellani Paolo , Alberghini Leonardo , Scapin Riccardo Miotti , Taccioli Cristian
Published: September 2021

GenBank files contain genomic data of sequenced living organisms. Here, we present GBRAP (GenBank Retrieving, Analyzing and Parsing software), a tool written in Python 3 that can be used to easily download, parse and analyze viral and bacterial GenBank files, even when contain more than one genomic sequence for each species. GBRAP can analyze more files simultaneously through single command-line parameters that give as output a single table showing the genomic characteristics of each organism. It is also able to calculate Shannon, LZSS (Lempel–Ziv–Storer–Szymanski) and topological entropy for both the entire genome and its constitutive elements such as genes, rRNAs, tRNAs, tmRNAs and ncRNAs together with Chargaff’s second parity rule scores obtained using different mathematical methods. Moreover, GBRAP can calculate, the number, the length and the nucleotides abundance of genomic components for each DNA strand and for the overlapping regions among the two complementary helixes. To our knowledge, this is the only software capable of providing this type of genomic analyses all together in a single tool, that, therefore can be used by the scientists interested in both genomics and evolutionary research.

Availability and implementation

The data underlying this article are available from the corresponding author on reasonable request.
Mitophagy enhancers against phosphorylated Tau-induced mitochondrial and synaptic toxicities in Alzheimer disease
Authors: Kshirsagar Sudhir , Sawant Neha , Morton Hallie , Reddy Arubala P. , Reddy P. Hemachandra
Published: September 2021

The purpose of our study is to determine the protective effects of mitophagy enhancers against phosphorylated tau (P-tau)-induced mitochondrial and synaptic toxicities in Alzheimer’s disease (AD). Mitochondrial abnormalities, including defective mitochondrial dynamics, biogenesis, axonal transport and impaired clearance of dead mitochondria are linked to P-tau in AD. Mitophagy enhancers are potential therapeutic candidates to clear dead mitochondria and improve synaptic and cognitive functions in AD. We recently optimized the doses of mitophagy enhancers urolithin A, actinonin, tomatidine, nicotinamide riboside in immortalized mouse primary hippocampal (HT22) neurons. In the current study, we treated mutant Tau expressed in HT22 (mTau-HT22) cells with mitophagy enhancers and assessed mRNA and protein levels of mitochondrial/synaptic genes, cell survival and mitochondrial respiration. We also assessed mitochondrial morphology in mTau-HT22 cells treated and untreated with mitophagy enhancers. Mutant Tau-HT22 cells showed increased fission, decreased fusion, synaptic & mitophagy genes, reduced cell survival and defective mitochondrial respiration. However, these events were reversed in mitophagy enhancers treated mTau-HT22 cells. Cell survival was increased, mRNA and protein levels of mitochondrial fusion, synaptic and mitophagy genes were increased, and mitochondrial fragmentation is reduced in mitophagy enhancers treated mTau-HT22 cells. Further, urolithin A showed strongest protective effects among all enhancers tested in AD. Our combination treatments of urolithin A + EGCG, addition to urolithin A and EGCG individual treatment revealed that combination treatments approach is even stronger than urolithin A treatment. Based on these findings, we cautiously propose that mitophagy enhancers are promising therapeutic drugs to treat mitophagy in patients with AD.
Preparing for a second attack: a lesion simulation study on network resilience after stroke
Authors: van Assche Mitsouko , Klug Julian , Dirren Elisabeth , Richiardi Jonas , Carrera Emmanuel
Published: September 2021

Background and Purpose

Does the brain become more resilient after a first stroke to reduce the consequences of a new lesion? Although recurrent strokes are a major clinical issue, whether and how the brain prepares for a second attack is unknown. This is due to the difficulties to obtain an appropriate dataset of stroke patients with comparable lesions, imaged at the same interval after onset. Furthermore, timing of the recurrent event remains unpredictable.

Methods

Here we used a novel clinical lesion simulation approach to test the hypothesis that resilience in brain networks increases during stroke recovery. 16 patients with a lesion restricted to the primary motor cortex were recruited. At 3 time points of the index event (10 days, 3 weeks, 3 months), we mimicked recurrent infarcts by deletion of nodes in brain networks (resting-state fMRI). Graph measures were applied to determine resilience (global efficiency) and wiring cost (mean degree) of the network.

Results

At 10 days and 3 weeks after stroke, resilience was similar in patients and controls. However, at 3 months, while motor function had fully recovered, resilience to clinically representative simulated lesions was higher compared to controls (cortical lesion p=0.012; subcortical: p=0.009; cortico-subcortical: p=0.009). Similar results were found after random (p=0.012) and targeted (p=0.015) attacks.

Conclusion

Our results suggest that, after a lesion, brain networks reconfigure to increase resilience to future insults. Lesion simulation is an innovative approach, which may have major implications for stroke therapy. Individualized neuromodulation strategies could be developed to foster resilient network reconfigurations after a first stroke to limit the consequences of future attacks.
The influence of objecthood on the representation of natural images in the visual cortex
Authors: Papale Paolo , Zuiderbaan Wietske , Teeuwen Rob R.M. , Gilhuis Amparo , Self Matthew W. , Roelfsema Pieter R. , Dumoulin Serge O.
Published: September 2021

Neurons in early visual cortex are not only sensitive to the image elements in their receptive field but also to the context determining whether the elements are part of an object or background. We here assessed the effect of objecthood in natural images on neuronal activity in early visual cortex, with fMRI in humans and electrophysiology in monkeys. We report that boundaries and interiors of objects elicit more activity than the background. Boundary effects occur remarkably early, implying that visual cortical neurons are tuned to features characterizing object boundaries in natural images. When a new image is presented the influence of the object interiors on neuronal activity occurs during a late phase of neuronal response and earlier when eye movements shift the image representation, implying that object representations are remapped across eye-movements. Our results reveal how object perception shapes the representation of natural images in early visual cortex.
Origin of electroneutrality in living system
Authors: Akbari Amir , Palsson Bernhard O.
Published: September 2021

Identifying the first chemical transformations, from which life emerged is a central problem in the theories of life’s origins. These reactions would likely have been self-sustaining and self-reproductive before the advent of complex biochemical pathways found in modern organisms to synthesize lipid membranes, enzymes, or nucleic acids. Without lipid membranes and enzymes, exceedingly low concentrations of the organic intermediates of early metabolic cycles in protocells would have significantly hindered evolvability. To address this problem, we propose a mechanism, where a positive membrane potential elevates the concentration of the organic intermediates. In this mechanism, positively charged surfaces of protocell membranes due to accumulation of transition metals generate positive membrane potentials. We compute steady-state ion distributions and determine their stability in a protocell model to identify the key factors constraining achievable membrane potentials. We find that (i) violation of electroneutrality is necessary to induce nonzero membrane potentials; (ii) strategies that generate larger membrane potentials can destabilize ion distributions; and (iii) violation of electroneutrality enhances osmotic pressure and diminishes reaction efficiency, thereby driving the evolution of lipid membranes, specialized ion channels, and active transport systems.

Significance

The building blocks of life are constantly synthesized and broken down through concurrent cycles of chemical transformations. Tracing these reactions back 4 billion years to their origins has been a long-standing goal of evolutionary biology. The first metabolic cycles at the origin of life must have overcome several obstacles to spontaneously start and sustain their nonequilibrium states. Notably, maintaining the concentration of organic intermediates at high levels needed to support their continued operation and subsequent evolution would have been particularly challenging in primitive cells lacking evolutionarily tuned lipid membranes and enzymes. Here, we propose a mechanism, in which the concentration of organic intermediates could have been elevated to drive early metabolic cycles forward in primitive cells with ion-permeable porous membranes under prebiotic conditions and demonstrate its feasibility in a protocell model from first principles.
Single shot detector application for image disease localization
Authors: Chopade Rushikesh , Stanam Aditya , Pawar Shrikant
Published: September 2021

Bounding box algorithms are useful in localization of image patterns. Recently, utilization of convolutional neural networks on X-ray images has proven a promising disease prediction technique. However, pattern localization over prediction has always been a challenging task with inconsistent coordinates, sizes, resolution and capture positions of an image. Several model architectures like Fast R-CNN, Faster R-CNN, Histogram of Oriented Gradients (HOG), You only look once (YOLO), Region-based Convolutional Neural Networks (R-CNN), Region-based Fully Convolutional Networks (R-FCN), Single Shot Detector (SSD), etc. are used for object detection and localization in modern-day computer vision applications. SSD and region-based detectors like Fast R-CNN or Faster R-CNN are very similar in design and implementation, but SSD have shown to work efficiently with larger frames per second (FPS) and lower resolution images. In this article, we present a unique approach of SSD with a VGG-16 network as a backbone for feature detection of bounding box algorithm to predict the location of an anomaly within chest X-ray image.
Relative timing of RSV epidemics in summer 2021 across the US was similar to a typical RSV season
Authors: Zheng Zhe , Warren Joshua L. , Artin Iris , Pitzer Virginia E. , Weinberger Daniel M.
Published: September 2021

We evaluated the timing of respiratory syncytial virus (RSV) epidemics in 2021 using Google search data. Despite the unusual out-of-season timing, the relative timing of RSV epidemics between states in 2021 shared a similar spatial pattern with typical RSV seasons. These insights can inform prophylaxis administration and planning of clinical trials.
An artificial intelligence system for predicting mortality in COVID-19 patients using chest X-rays: a retrospective study
Authors: Nanivadekar Avinash , Zirpe Kapil , Dwivedi Ashutosh , Patel Rajan , Pant Richa , Gupte Tanveer , Lokwani Rohit , Shende Dinesh , Kulkarni Viraj , Kharat Amit
Published: September 2021

Background

Early prediction of disease severity in COVID-19 patients is essential. Chest X-ray (CXR) is a faster, widely available, and less expensive imaging modality that may be useful in predicting mortality in COVID-19 patients. Artificial Intelligence (AI) may help expedite CXR reading times, and improve mortality prediction. We sought to develop and assess an artificial intelligence system that used chest X-rays and clinical parameters to predict mortality in COVID-19 patients.

Methods

A retrospective study was conducted in Ruby Hall Clinic, Pune, India. The study included patients who had a positive real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test for COVID-19 and at least one available chest X-ray at the time of their initial presentation or admission. Features from CXR images and clinical parameters were used to train the Random Forest model.

Results

Clinical data from a total of 201 patients was assessed retrospectively. The average age of the cohort was 51.4±14.8 years, with 29.4% of the patients being over the age of 60. The model, which used CXRs and clinical parameters as inputs, had a sensitivity of 0.83 [95% CI: 0.7, 0.95] and a specificity of 0.7 [95% CI: 0.64, 0.77]. The area under the curve (AUC) on receiver operating characteristics (ROC) was increased from 0.74 [95% CI: 0.67, 0.8] to 0.79 [95% CI: 0.72, 0.85] when the model included features of CXRs in addition to clinical parameters.

Conclusion

An Artificial Intelligence (AI) model based on CXRs and clinical parameters demonstrated high sensitivity and can be used as a rapid and reliable tool for COVID-19 mortality prediction.