bluuebunny/crossref_metadata_2025 huggingface dataset:
Sero-epidemiology study of hepatitis B virus surface antibodies from 2017 to 2019 among Chinese young adults in Hunan Province
Authors: Xie Ming , Quan Hongjiao , Zeng Yuan , Yuan Shuqian , Liu Yinyue , Yang Yide
Published: August 2021

Background:

Data on the epidemiology characteristics of hepatitis B surface antibodies (anti-HBs) are lacking among central southern undeveloped areas of China, especially for young adults. This study aims to demonstrate the sero-epidemiology characteristics of HBsAb among young adults.

Aims:

The aim of this study is to demonstrate the epidemiological characteristics in prevalence of serum anti-HBs in college students of a university in Hunan Province, China.

Methods:

Data were derived from the health records (including serum HBsAb data) among freshmen of a university from 2017 to 2019 in Hunan Province, China.

Results:

A total of 13,426 freshmen with complete data who were born in Hunan Province were collected. The 3-year total prevalence of anti-HBs in freshmen was 44.75% with no statistically significant sex difference, the prevalence of anti-HBs is 46.93%, 53.13%, and 34.79% for 2017, 2018, and 2019, respectively. There are significant geographic differences of prevalence of anti-HBs in freshmen from different areas. The lowest prevalence of anti-HBs was 31.80% in freshmen from Xiangtan, and the highest prevalence of anti-HBs was 53.10% in freshmen from Yongzhou.

Conclusion:

The prevalence of serum anti-HBs among the freshmen in Hunan from 2017 to 2019 is much lower than the average national level, and the prevalence in 2019 is significantly lower than that in 2017 and 2019. There are significant differences in different time and areas of the prevalence of anti-HBs. There is a necessity to carry out area-specific intensive immunization plan in a timely manner among young population in Hunan Province, China.
A survey of PM2.5 preventive behavioral intention and related factors among community elderly in Northern Taiwan
Authors: Weng Yu-Ling , Liang Chin-Chia , Tseng Chie-Chien , Lee Shih-Yi , Yeh Gwo-Liang
Published: August 2021

Population aging and air pollution are global concerns. The purpose of this study is to explore the relationship among particulate matter with a diameter of 2.5 μm or less (PM2.5) knowledge, PM2.5 preventive attitude, and PM2.5 preventive behavioral intention in the elderly.

A cross-sectional survey design was applied in this study, including usage intention and snowball sampling. A total of 617 elderly people aged over 65 participated, and the collected data were quantitatively analyzed.

The results showed that the mean score of PM2.5 knowledge of the elderly was 10.34 (79.53%) with the standard deviation (SD) of 3.42, the mean score of PM2.5 preventive attitude was 4.58 (91.60%) with SD of 0.49, and the mean score of PM2.5 preventive behavioral intention was 4.72 (94.40%) with SD of 0.40. Elderly people's characteristics regarding PM2.5 knowledge and PM2.5 preventive attitude explained 22% (adjusted R
2 = 0.22, F = 30.44, P < .001) of the variance in PM2.5 preventive behavioral intention.

It is concluded that we found no difference in PM2.5 knowledge, PM2.5 preventive attitude, or PM2.5 preventive behavioral intention among the elderly with or without chronic diseases. In our opinion, health education regarding the threat of PM2.5 to the health of the elderly should be strengthened, to enhance their knowledge, preventive attitude, and preventive behavioral intention of PM2.5.
Disseminated nocardiosis caused by Nocardia farcinica in a patient with colon cancer
Authors: Lee Eung Kyum , Kim Jin , Park Dong-Hyuk , Lee Chang Kyu , Kim Sun Bean , Sohn Jang Wook , Yoon Young Kyung
Published: August 2021

Rationale:

Nocardiosis is an uncommon and potentially life-threatening infection that usually affects immunocompromised hosts. No clinical guidelines have been established for managing this rare disease, and the optimal treatment modality remains unclear. Nocardia farcinica, a relatively infrequent pathogen of nocardiosis, causes a clinically aggressive infection. In addition to our patient data, our search of the literature for patients who presented with empyema caused by N. farcinica will provide fundamental information for optimal treatment modalities.

Patient concerns:

A 64-year-old man was diagnosed with empyema, 4 days following surgery for sigmoid colon cancer. Brain lesions were evaluated only after N. farcinica was isolated and identified as the causative pathogen through repeated culture tests.

Diagnoses:

N. farcinica was isolated from the pleural effusion and confirmed as the pathogen through 16S rRNA sequencing.

Interventions:

The patient was successfully treated with tube thoracotomy, neurosurgical evacuation, and a combination of trimethoprim/sulfamethoxazole plus imipenem. Long-term antibiotic therapy was required to prevent recurrence.

Outcomes:

Pyothorax showed a good clinical response to antimicrobial therapy and drainage of pleural effusion, whereas brain abscess did not respond to medical therapy and required surgery. The patient eventually recovered and continued chemotherapy as treatment for sigmoid colon cancer.

Lessons:

Although extremely rare, this report demonstrates the importance of considering Nocardia infection as the differential diagnosis in immunocompromised patients who present with empyema. In particular, because of the N. farcinica infection's tendency to spread and the resistance of the organism to antibiotics, aggressive evaluation of metastatic lesions and standardized support from microbiological laboratories are important. Surgery may be required in some patients with brain abscesses to improve the chance of survival.
Sinus pause during nerve integrity monitoring tube insertion following anesthetic induction with a low-dose neuromuscular blocking agent
Authors: Byun Sung-Hye , Jeon Jae-Min
Published: August 2021

Rationale:

Nerve integrity monitoring (NIM) tubes are commonly used in thyroid surgery to prevent recurrent laryngeal nerve injury. To achieve the optimal electromyographic signal for NIM as intraoperative neural monitoring (IONM), the neuromuscular blocking agent (NMBA) dose should be low. The use of a low-dose NMBA increases the anesthetic and analgesic agent dose required to attenuate the laryngeal reflex during intubation. In addition, since the NMBA onset time is delayed, depending on the situation, anesthesia may become excessively deep or shallow before intubation.

Patient's concern:

A 51-year-old woman scheduled for thyroid lobectomy received 0.3 mg/kg of rocuronium. Three minutes later, when the NIM tube was inserted through the vocal cord, the patient's heart rate (HR) was undetectable for 2 seconds.

Diagnosis:

We suspected that the use of a high-dose anesthetic agent and remifentanil or the laryngocardiac reflex induced the sinus pause.

Interventions:

To maintain the anesthetic depth, we administered 6 vol% of desflurane. Because the patient's systolic blood pressure was 70 mmHg and HR was 30 beats/min, we discontinued the remifentanil infusion and administered 8 mg of ephedrine.

Outcomes:

The patient's vital signs recovered to normal levels. Subsequently, there were no episodes of bradycardia or arrhythmia.

Conclusion:

Sinus pause or severe bradycardia may occur due to the laryngocardiac reflex or the administration of a high-dose anesthetic and analgesic agent during tracheal intubation in patients who received a low-dose NMBA for IONM induction using an NIM tube. Anesthesiologists should be aware of these risks and take precautions to maintain adequate anesthesia, be prepared to administer vasoactive drugs to increase the blood pressure and HR if needed, and, if possible, intravenously administer lidocaine to attenuate the laryngeal reflex during intubation.
Bilateral Trichosporon asahii keratitis after ptosis correction
Authors: Shin Jeongah , Son Woo Young , Cho Kyong Jin , Rho Chang Rae
Published: August 2021

Rationale:

Fungal keratitis (FK) is a severe vision-threatening disease that can lead to corneal perforation or endophthalmitis despite proper treatment. It is important to diagnose the disease promptly due to its indolent nature and disproportionate disease symptoms. Trichosporon asahii is reported rarely as the causative organism of FK. We report a case of highly unusual bilateral T asahii keratitis following ptosis surgery.

Patient concerns:

An 86-year-old female underwent bilateral levator resection surgery for ptosis. Postoperatively, the patient complained of gradually worsening bilateral ocular pain and a decrease in visual acuity associated with a chronic non-healing epithelial defect.

Diagnoses:

Both eyes of the patient were evaluated using best-corrected visual acuity, intraocular pressure, slit-lamp examination, fundus examination, and corneal culture. Multifocal deep stromal infiltrates were found in both corneas. Cultures from both corneal ulcers revealed growth of T asahii. Optical coherence tomographic examination showed bilateral macular edema.

Interventions:

The patient was treated with revisional ptosis surgery, an antifungal agent for the corneal ulcer, and intravitreal injection of steroid for macular edema.

Outcomes:

Both eyes recovered well. Her best-corrected visual acuity improved from 20/200 to 20/40 in the right eye and from 20/100 to 20/40 in the left eye.

Lessons:

FK can develop in the cornea when certain risk factors are present, including recent lid surgery, chronic keratitis, and steroid eye drop use. Identification and correction of risk factors can be beneficial in the treatment of FK.
Impact of chronic kidney disease on the prognosis of transcatheter aortic valve replacement in patients with aortic stenosis
Authors: Wang Jialu , Liu Shidong , Han Xiangxiang , Wan Zunhui , Chen Yang , Chen Hao , Song Bing
Published: August 2021

Background:

The prognosis of patients with aortic stenosis, in conjunction with chronic kidney disease (CKD), after transcatheter aortic valve replacement (TAVR) remains unclear. This study assessed the impact of CKD, and different stages of CKD, on prognosis of patients undergoing TAVR.

Methods:

The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement guidelines. As of June 2021, we performed a comprehensive literature search on studies related to CKD and TAVR, using databases such as PubMed, Embase, Cochrane Library, and Web of Science. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. Then, Stata 15.0 software was used for meta-analysis.

Results and Conclusion:

The purpose of this study was to evaluate the effect of CKD and different stages of CKD on the prognosis of patients with TAVR. It is hoped to provide a comprehensive reference for clinical practice and related clinical trials in the future.
Efficacy and safety of acupuncture for senile insomnia
Authors: Wu Jiuru , Shi Yan , Wang Xichen , Dong Xiukun , Liu Xinyu , Wang Guojian , Hu Yinghua
Published: August 2021

Background:

Senile insomnia seriously affects the quality of life of the elderly. With the increase of the proportion of insomnia in the elderly, compared with the elderly with normal sleep quality, the elderly with long-term insomnia are more likely to have dizziness, fatigue, and decreased immunity. Acupuncture has shown good effects in the treatment of insomnia. At present, there is a lack of systematic review on acupuncture in the treatment of senile insomnia. We conduct this study to evaluate the efficacy and safety of acupuncture in the treatment of senile insomnia.

Methods:

We will search Chinese and English databases: China National Knowledge Infrastructure, Chinese Scientific and Journal Database, Wan Fang database (Wanfang), Chinese Biomedical Literature Database, PubMed, EMBASE, Cochrane library to identify articles of randomized clinical trials of acupuncture for senile insomnia. All above electronic databases will be searched from inception to September 1, 2021. RevMan 5.3 software will be used to conduct this systematic review.

Results:

The study will prove the efficacy and safety of acupuncture for senile insomnia.

Conclusion:

We plan to submit this systematic review to a peer-reviewed journal.

INPLASY registration number:

INPLASY202160106.
Risk factors for acute kidney injury in critically ill patients with torso injury
Authors: Sul Young Hoon , Lee Jin Young , Kim Se Heon , Ye Jin Bong , Lee Jin Suk , Yoon Su Young , Choi Jung Hee
Published: August 2021

Acute kidney injury (AKI) is common in trauma patients and associated with poor outcomes. Identifying AKI risk factors in trauma patients is important for risk stratification and provision of optimal intensive care unit (ICU) treatment. This study identified AKI risk factors in patients admitted to critical care after sustaining torso injuries.

We performed a retrospective chart review involving 380 patients who sustained torso injuries from January 2016 to December 2019. Patients were included if they were aged >15 years, admitted to an ICU, survived for >48 hours, and had thoracic and/or abdominal injuries and no end-stage renal disease. AKI was defined according to the Kidney Disease Improving Global Outcomes definition and staging system. Clinical and laboratory variables were compared between the AKI and non-AKI groups (n = 72 and 308, respectively). AKI risk factors were assessed using multivariate logistic regression analysis.

AKI occurred in 72 (18.9%) patients and was associated with higher mortality than non-AKI patients (26% vs 4%, P < .001). Multivariate logistic regression analysis identified bowel injury, cumulative fluid balance >2.5 L for 24 hours, lactate levels, and vasopressor use (adjusted odds ratio: 2.953, 2.058, 1.170, and 2.910; 95% confidence interval: 1.410–6.181, 1.017–4.164, 1.019–1.343, and 1.414–5.987; P = .004, .045, .026, and .004, respectively) as independent risk factors for AKI.

AKI in patients admitted to the ICU with torso injury had a substantial mortality. Recognizing risk factors at an early stage could aid risk stratification and provision of optimal ICU care.
Values of ultrasound for diagnosis and management of insulin-induced lipohypertrophy
Authors: Wang Wei , Huang Rong , Chen Yang , Tu Mei
Published: August 2021

The aim of this study was to explore the values of ultrasound for diagnosis and management of insulin-induced lipohypertrophy and further analyzing the impact of body mass index and subcutaneous fat thickness on ultrasound manifestations of lipohypertrophy.

In this 3-month, prospective cohort study, a total of 162 patients with diabetes who used insulin therapy more than 1 year with unknown lipohypertrophy status were enrolled into this study. Demographic information, assessment of glycemic control and insulin injection technique were evaluated. Physical and ultrasound examination were separately performed to detect lipohypertrophy by a team of diabetes educator nurses or ultrasonographer in a blinded fashion. Patients with lipohypertrophy received insulin injection technique education based on ultrasound examination and Chinese guideline.

Ultrasound examination detected 41.1% more patients (74.1% vs 52.5%; P < .001) with lipohypertrophy and 61.2% more lesions (216 vs 134; P < .001) than physical examination. Glycosylated hemoglobin A1c and fasting blood glucose were significantly decreased in patients with lipohypertrophy or subclinical lipohypertrophy (lipohypertrophy without visual and palpation changes) after receiving insulin injection technique education based on ultrasound examination and Chinese guideline than baseline at 3 months (P < .001). The proportion of lesions with ultrasound manifestation 2 (distortion of surrounding connective tissue) in obese and STF (>15 mm) groups were no more than 50% and showed a decreased trend with increased subcutaneous fat thickness and body mass index (P < .001).

Lipohypertrophy has characteristic ultrasound manifestations which can detect more accurate results than palpation alone and provide detailed information to promote effective education on lipohypertrophy management, thereby improving glycemic control.
Mediating effects of meaning in life on the relationship between general self-efficacy and nursing professional commitment in nursing students
Authors: Cheng Linan , Chen Qian , Zhang Fengying
Published: August 2021

Meaning in life (MiL) is regarded as a valuable indicator of positive functioning in terms of an understanding of one's purpose in life, well-being, and professional commitment. As such, it is important to improve MiL for the stability of nursing staff. General self-efficacy is a significant predictor of both MiL and nursing professional commitment. Nursing professional commitment is key for both the stability of nursing staff and the provision of excellent health care. Few scholars have investigated the relationship between general self-efficacy and nursing professional commitment. In particular, a possible mediating effect of MiL has not been fully explored in nursing students.

We aimed to examine the association between general self-efficacy and MiL among nursing students and to determine whether MiL mediates the relationship between general self-efficacy and nursing professional commitment for Chinese nursing students.

A cross-sectional descriptive design was used. Between June and September 2019, 710 Chinese nursing students from 2 colleges completed the Meaning in Life Scale (MiLS), General Self-Efficacy Scale (GSES), and Nursing Professional Commitment Scale (NPCS). Data were analyzed using structural equation modeling (SEM) and SPSS (version 23.0, IBM Corp, Armonk, NY).

The mean MiL score was above the moderate level (M = 52.55, SD = 9.79). However, the mean scores of self-efficacy and nursing professional commitment were relatively low. Self-efficacy was positively related to MiL (B = 0.46, P < .01), and MiL was positively related to nursing professional commitment (B = 0.37, P < .01). However, self-efficacy was not related to nursing professional commitment (B = 0.12, P = .01). We therefore suggest that MiL has a complete mediating role between self-efficacy and nursing professional commitment among Chinese nursing students.

In this study, we confirmed the complete mediation of nursing professional commitment by MiL in nursing students, thus providing scientific evidence that could be beneficial for the development of interventions to increase nursing professional commitment.
Dissociative symptoms with intravenous ketamine in treatment-resistant depression exploratory observational study
Authors: Włodarczyk Adam , Cubała Wiesław J. , Gałuszko-Węgielnik Maria , Szarmach Joanna
Published: August 2021

There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety and tolerability concerns arise regarding adverse drug reactions and specific subpopulations. This paper aims to investigate the relationship between dissociative and psychometric measures in course of intravenous ketamine treatment in TRD inpatients with major depressive disorder and bipolar disorder.

This study result represents safety data in a population of 49 inpatients with major depressive disorder and bipolar disorder subjects receiving eight 0.5 mg/kg of ketamine intravenous infusions, with a duration of 40 min each, as an add-on treatment to standard-of-care pharmacotherapy, registered in the naturalistic observational protocol of the tertiary reference unit for mood disorders (NCT04226963). The safety psychometrics assessed dissociation and psychomimetic symptomatology with the Clinician-Administered Dissociative States Scale (CADSS) the Brief Psychiatric Rating Scale (BPRS).

The significant differences in CADSS scores between measurements in course of the treatment were observed (P = .003). No significant differences between BPRS measurements were made after infusions. In each case, both BPRS and CADSS values dropped to the “absent” level within 1 hour from the infusion. Neither CADSS nor BPRS scores were associated with the treatment outcome.

The study demonstrates a good safety profile of intravenous ketamine as an add-on intervention to current psychotropic medication in TRD. The abatement of dissociation was observed in time with no sequelae nor harm. The study provides no support for the association between dissociation and treatment outcome.

This study may be underpowered due to the small sample size. The protocol was defined as a study on acute depressive symptomatology without blinding.
Efficacy of Xpert MTB/RIF Ultra in diagnosing tuberculosis meningitis
Authors: Shen Yanqin , Yu Guocan , Zhao Wuchen , Lang Yazhen
Published: August 2021

Background:

This study aimed to assess whether Xpert MTB/RIF Ultra (Xpert Ultra) can effectively diagnose tuberculosis meningitis (TBM) and to simultaneously compare its effectiveness with Xpert in diagnosing TBM in the same population.

Methods:

On August 12, 2020, Wanfang Database, China National Knowledge Infrastructure, Embase, Cochrane Library, and PubMed were searched for studies evaluating the diagnostic accuracy of Xpert Ultra for TBM. Then, we assessed the efficacy of Xpert Ultra against a composite reference standard and culture. If applicable, we also examined the diagnostic efficacy of Xpert in the same population. Heterogeneity was then explored by meta-regression, subgroup, and sensitivity analyses.

Results:

Six studies containing 601 specimens reported the diagnostic efficacy of Xpert Ultra for TBM, with a composite reference standard. No study had compared the efficacy between Xpert Ultra and culture. The pooled sensitivity of Xpert Ultra was 64% (95% confidence interval [CI]: 45–80), and the I
2 value was 86% (95% CI: 76–96); its specificity for TBM was consistently 100%. In the same population, 5 studies compared the diagnostic efficacy between Xpert Ultra and Xpert for TBM. The pooled sensitivity of Xpert Ultra and Xpert was 68% (95% CI: 46–84; I
2 = 87%) and 37% (95% CI: 25–50; I
2 = 72%), respectively. The studies were significantly heterogeneous in terms of sensitivity but not heterogeneous in specificity.

Conclusions:

Xpert Ultra was more sensitive than Xpert, but both were specific (100%). Therefore, Xpert Ultra had an excellent diagnostic efficacy for TBM, and it could be the preferred initial test for TBM.
A case study of overfeeding 3 different diets
Authors: Feltham Sam , Westman Eric C.
Published: August 2021

Purpose of review

Quality or quantity of food has been at the heart of the diet debate for decades and will seemingly continue for many to come unless tightly controlled studies are conducted. To our knowledge, there has never been an overfeeding study comparing the effects of multiple diets.

Recent findings

This study reports a case study of an individual who ate 5800 Calories per day of 3 different diets for 21 days at a time. The 3 different diets were low-carb, low-fat, and very-low-fat vegan. The weight gain over 21 days was 1.3 kg for low-carb, 7.1 kg for low-fat, and 4.7 kg for very-low-fat vegan.

In this n-of-1 study, consuming 5800 Calories/day of 3 different diets for 21 days did not lead to the same amount of weight gain. Further research should be conducted on how the human body gains weight with an emphasis on how different foods affect physiology. If these findings are replicated, there would be many ramifications for obesity treatment and healthcare guidelines.
Antimicrobial resistance in Bacillus-based biopesticide products
Authors: Kaze Mo , Brooks Lauren , Sistrom Mark
Published: August 2021

The crisis of antimicrobial resistant bacterial infections is one of the most pressing public health issues. Common agricultural practices have been implicated in the generation of antimicrobial resistant bacteria. Biopesticides, live bacteria used for pest control, are non-pathogenic and considered safe for consumption. Application of bacteria-based pesticides to crops in high concentrations raises the possibility of unintentional contributions to the movement and generation of antimicrobial resistance genes in the environment. However, the presence of clinically relevant antimicrobial resistance genes and their resistance phenotypes are currently unknown. Here we use a combination of multiple bioinformatic and microbiological techniques to define resistomes of widely used biopesticides and determine how the presence of suspected antimicrobial resistance genes translates to observable resistance phenotypes in several biopesticide products. Our results demonstrate that biopesticide products are reservoirs of clinically relevant antimicrobial resistance genes and bear resistance to multiple drug classes.
SARS-CoV-2 antibody changes in patients receiving COVID-19 convalescent plasma from normal and vaccinated donors
Authors: Leon Judith , Merrill Anna E. , Rogers Kai , Kurt Julie , Dempewolf Spencer , Ehlers Alexandra , Jackson J. Brooks , Knudson C. Michael
Published: August 2021

Background and Objectives

Vaccination has been shown to stimulate remarkably high antibody levels in donors who have recovered from COVID-19. Our objective was to examine patient antibody responses following COVID-19 Convalescent Plasma (CCP) transfusion and compare responses to CCP from vaccinated and nonvaccinated donors.

Materials and methods

Plasma samples were obtained from 25 recipients of CCP and COVID-19 antibody levels measured before and after CCP treatment. Factors that effect antibody levels were examined.

Results

In the 21 patients who received CCP from nonvaccinated donors, only modest increases in antibody levels were observed. Patients who received two units were more likely to seroconvert than those receiving just one unit. The strongest predictor of changes in patient antibody level was the CCP dose. Using patient plasma volume and donor antibody level, the post-transfusion antibody level could be predicted with remarkable accuracy. In contrast, the 4 patients who received CCP from vaccinated donors all had dramatic increases in antibody levels following transfusion of a single unit. In this subset of recipients, antibody levels observed after transfusion of CCP were comparable to those seen in donors who had fully recovered from COVID-19.

Conclusion

If available, CCP from vaccinated donors with very high antibody levels should be used. CCP from vaccinated donors increases patient antibody levels much more than 1 or 2 units of CCP from unvaccinated donors.
Salivary proteome of aphthous stomatitis reveals the participation of vitamin metabolism, nutrients, and bacteria
Authors: Hernández-Olivos Romina , Muñoz Mariagrazia , Núñez Esteban , Camargo-Ayala Paola Andrea , Garcia-Huidobro Jenaro , Pereira Alfredo , Nachtigall Fabiane M. , Santos Leonardo S. , Rivera César
Published: August 2021

There are currently no preventative options for recurrent aphthous stomatitis, and the only available treatments are palliative. This is partly due to a poor understanding of its etiopathogenesis. In this case-control study, we characterized the salivary proteome of patients with recurrent aphthous stomatitis in the presence and absence of lesions. Through mass spectrometry-based proteomics and bioinformatics tools, we identified that the presence of oral ulcers is associated with several specific biological processes, including the metabolic pathways of vitamin B9, B12, nitrogen, selenium, and the bacterium Neisseria meningitidis. These changes occurred only in the presence of clinically visible lesions, and there were no relevant differences between patients in anatomical regions unaffected by ulcers. Additionally, using western blot and ELISA assays, we verified that carbonic anhydrase 1 (CA1, UniProtKB - P00915, CAH1_HUMAN) and hemoglobin subunit beta (HBB, UniProtKB - P68871, HBB_HUMAN) proteins are highly expressed during the ulcerative and remission phases of recurrent aphthous stomatitis. Our results cumulatively support saliva as an indicator of the pathophysiological changes, which occur during the clinical course of lesions. From a clinical perspective, we suggest that recurrent aphthous stomatitis is a condition triggered by temporary biological changes in people with lesions.
Novel Driver Strength Index highlights important cancer genes in TCGA PanCanAtlas patients
Authors: Belikov Aleksey V. , Otnyukov Danila V. , Vyatkin Alexey D. , Leonov Sergey V.
Published: August 2021

Elucidating crucial driver genes is paramount for understanding the cancer origins and mechanisms of progression, as well as selecting targets for molecular therapy. Cancer genes are usually ranked by the frequency of mutation, which, however, does not necessarily reflect their driver strength. Here we hypothesize that driver strength is higher for genes that are preferentially mutated in patients with few driver mutations overall, because these few mutations should be strong enough to initiate cancer. We propose a formula to calculate the corresponding Driver Strength Index (DSI), as well as the Normalized Driver Strength Index (NDSI), the latter completely independent of the overall gene mutation frequency. We validate these indices using the largest database of human cancer mutations – TCGA PanCanAtlas, multiple established algorithms for cancer driver prediction (2020plus, CHASMplus, CompositeDriver, dNdScv, HotMAPS, OncodriveCLUSTL, OncodriveFML) and four custom computational pipelines that integrate driver contributions from SNA, CNA and aneuploidy at the patient-level resolution. We demonstrate that DSI and especially NDSI provide substantially different rankings of genes as compared to frequency approach. For example, NDSI prioritized members of specific protein families, including G proteins GNAQ, GNA11 and GNAS, isocitrate dehydrogenases IDH1 and IDH2, and fibroblast growth factor receptors FGFR2 and FGFR3. KEGG analysis shows that top NDSI-ranked genes comprise EGFR/FGFR2/GNAQ/GNA11 – NRAS/HRAS/KRAS – BRAF pathway, AKT1 – MTOR pathway, and TCEB1 – VHL – HIF1A pathway. NDSI does not seem to correlate with the number of protein-protein interactions. We share our software to enable calculation of DSI and NDSI for outputs of any third-party driver prediction algorithms or their combinations.
Development of Goal Management Training+ (GMT+) for Methamphetamine Use Disorder Through Collaborative Design: A Process Description
Authors: Anderson Alexandra C. , Robinson Alex H. , Potter Eden , Kerley Bronte , Flynn Daphne , Lubman Dan I. , Verdejo-García Antonio
Published: August 2021

Background

Methamphetamine use disorder (MUD) is associated with executive dysfunctions, which are linked with poorer treatment outcomes including earlier drop out and relapse. However, current treatments for MUD do not address executive functions. Goal Management Training (GMT) is an evidence-based cognitive remediation program for executive dysfunction but required modifications to enhance its relevance and application within addiction treatment settings. This study aimed to 1) tailor GMT to the key cognitive deficits and typical treatment duration of MUD; 2) explore consumers’ (people with MUD) engagement with the revised program; 3) implement a protocol of the program with consumers; and 4) present the manualised standard administration to clinical service providers.

Methods

We followed the Medical Research Council Complex Interventions Framework and employed an evidence- and person-based intervention development process. We used a four-phased approach and collaborated with neuropsychology experts, design researchers in healthcare, consumers with MUD, and clinical service providers. Each aim was addressed in a separate study phase; including content refinement and review with neuropsychology experts (phase 1), intervention design and collaboration with consumers (phase 2), prototype development and review with consumers (phase 3), and final program modifications and review with clinical stakeholders (phase 4).

Results

Findings from phase 1 indicated support for targeting four cognitive processes (attention, impulse control, goal setting, and decision-making). Key feedback included the need to help habitualise program strategies and guide consumers in applying them in emotionally salient situations. Findings from phases 2 and 3 indicated consumer support for the program strategies and materials but highlighted the need to further enhance the personal relevance of specific content and journal activities. Findings from phase 4 provided overall clinical support for the revised program but indicated an opportunity to minimise unintended effects. We present the intervention materials for the revised program, Goal Management Training+ (GMT+), in line with TIDieR guidelines.

Conclusions

GMT+ targets tailored cognitive processes, includes reimagined materials and activities, and is sensitive to the clinical needs of people with MUD. Our intervention development process was important for informing the training components, design and intervention materials, and indicating initial acceptability prior to conducting a clinical trial.
Exploring the Relationship of Rush Hour Period and Fatal and Non-Fatal Crash Injuries in The U.S.: A Systematic Review and Meta-Analysis
Authors: Adeyemi Oluwaseun John , Arif Ahmed , Paul Rajib
Published: August 2021

Road crashes are preventable causes of morbidity and mortality. In the U.S., substantial crashes occur during the rush hour period. The rush hour represents the period of the day during which the density of humans and vehicles in the road environment is highest. In the U.S., the rush hour period is bi-modal, occurring in the morning and the afternoon, at times that vary by state and urban-rural status. This systematic review and meta-analysis aimed to evaluate the association between the rush hour period and fatal and non-fatal crash injuries. Selected articles were limited to peer-reviewed full-text articles that measured crash injury as an outcome and rush hour as either a predictor, covariate, stratification, or a control variable. A total of 13 articles were identified for systematic review and seven articles were included in the meta-analysis. Across the selected studies, the rush-hour period signified the period of “peak traffic flow.” During the rush hour period, aggressive driving behavior, truck driving, bicycle riding, and precipitation were associated with increased crash events or crash injuries. Across the seven studies included in the meta-analysis, the effective sample size was 220,471. The rush-hour period was associated with a 41% increased risk of fatal crash injury (Pooled RR: 1.41; 95% CI: 1.35 - 1.48). The morning and afternoon rush hour periods were associated with 40% (Pooled RR: 1.40; 95% CI: 1.13-1.67) and 27% (Pooled RR:1.27; 95% CI: 1.10-1.44) increased crash injury risk, respectively. The rush hour period, though less commonly studied as a predictor of fatal and non-fatal crash injuries, represents an important domain in need of crash injury prevention attention. The knowledge of the pattern of crash injuries, as it varies across countries, states, regions, and county can inform policy and intervention, in the presence of competing public health needs.
Learning the mutational landscape of the cancer genome
Authors: Sherman Maxwell A. , Yaari Adam , Priebe Oliver , Dietlein Felix , Loh Po-Ru , Berger Bonnie
Published: August 2021

An ongoing challenge to better understand and treat cancer is to distinguish neutral mutations, which do not affect tumor fitness, from those that provide a proliferative advantage. However, the variability of mutation rates has limited our ability to model patterns of neutral mutations and therefore identify cancer driver mutations. Here, we predict cancer-specific mutation rates genome-wide by leveraging deep neural networks to learn mutation rates within kilobase-scale regions and then refining these estimates to test for evidence of selection on combinations of mutations by comparing observed to expected mutation counts. We mapped mutation rates for 37 cancer types and used these maps to identify new putative drivers in understudied regions of the genome including cryptic alternative-splice sites, 5’ untranslated regions and infrequently mutated genes. These results, available for exploration via web interface, indicate the potential for high-resolution neutral mutation models to empower further driver discovery as cancer sequencing cohorts grow.
TAS-Seq: a robust and sensitive amplification method for bead-based scRNA-seq
Authors: Shichino Shigeyuki , Ueha Satoshi , Hashimoto Shinichi , Ogawa Tatsuro , Aoki Hiroyasu , Wu Bin , Chen Chang-Yu , Kitabatake Masahiro , Ouji-Sageshima Noriko , Sawabata Noriyoshi , Kawaguchi Takeshi , Okayama Toshitugu , Sugihara Eiji , Hontsu Shigeto , Ito Toshihiro , Iwata Yasunori , Wada Takashi , Ikeo Kazuho , Sato Taka-aki , Matsushima Kouji
Published: August 2021

Single-cell RNA-sequencing (scRNA-seq) is valuable for analyzing cellular heterogeneity. Cell composition accuracy is critical for analyzing cell–cell interaction networks from scRNA-seq data. We developed terminator-assisted solid-phase cDNA amplification and sequencing (TAS-Seq) for scRNA-seq based on a terminator, terminal transferase, and nanowell/bead-based scRNA-seq platform; TAS-Seq showed high tolerance to variations in the terminal transferase reaction, which complicate the handling of existing terminal transferase-based scRNA-seq methods. In murine and human lung samples, TAS-Seq yielded scRNA-seq data that were highly correlated with flow-cytometric data, showing higher gene-detection sensitivity and more robust detection of important cell–cell interactions and expression of growth factors/interleukins in cell subsets than 10X Chromium v2 and Smart-seq2. Expanding TAS-Seq application will improve understanding and atlas construction of lung biology at the single-cell level.
IMPDH1 retinal variants control filament architecture to tune allosteric regulation
Authors: Burrell Anika L , Nie Chuankai , Said Meerit , Simonet Jacqueline C , Fernández-Justel David , Johnson Matthew C , Quispe Joel , Buey Rubén M , Peterson Jeffrey R , Kollman Justin M
Published: August 2021

IMP dehydrogenase (IMPDH), a key regulatory enzyme in purine nucleotide biosynthesis, dynamically assembles filaments in response to changes in metabolic demand. Humans have two isoforms: IMPDH2 filaments reduce sensitivity to feedback inhibition by the downstream product GTP, while IMPDH1 assembly remains uncharacterized. IMPDH1 plays a unique role in retinal metabolism, and point mutants cause blindness and disrupt GTP regulation. Here, in a series of cryo-EM structures we show that IMPDH1 assembles polymorphic filaments with different assembly interfaces in active and inhibited states. Retina-specific splice variants introduce structural elements that reduce sensitivity to GTP inhibition, including stabilization of the active filament form. Finally, we show that IMPDH1 disease mutations fall into two classes: one disrupts GTP regulation and the other has no in vitro phenotype. These findings provide a foundation for understanding the role of IMPDH1 in retinal function and disease and demonstrate the diverse mechanisms by which metabolic enzyme filaments are allosterically regulated.
Altered low frequency brain rhythms precede changes in gamma power during tauopathy
Authors: Rodrigues Fabio R. , Papanikolaou Amalia , Holeniewska Joanna , Phillips Keith G. , Saleem Aman B. , Solomon Samuel G.
Published: August 2021

Alzheimer’s disease and other dementias are associated with disruptions of electrophysiological brain activity, including low frequency and gamma rhythms. Many of these dementias are also associated with the malfunction of the membrane associated protein tau. Tauopathy disrupts neuronal function and the stability of synapses and is a key driver of neurodegeneration. Here we ask how brain rhythms are affected by tauopathy, at different stages of its progression. We performed local field potential recordings from visual cortex of rTg4510 and control animals at early stages of neurodegeneration (5 months) and at a more advanced stage where pathology is evident (8 months). We measured brain activity in the presence or absence of external visual stimulation, and while monitoring pupil diameter and locomotion to establish animal behavioural states. At 5 months, before substantial pathology, we found an increase in low frequency rhythms during resting state in tauopathic animals. This was because tauopathic animals entered intermittent periods of increased neural synchronisation, where activity across a wide band of low frequencies was strongly correlated. At 8 months, when the degeneration was more advanced, the increased synchronisation and low frequency power was accompanied by a reduction in power in the gamma range, with diverse effects across different components of the gamma rhythm. Our results indicate that slower rhythms are impaired earlier than gamma rhythms in tauopathy, suggesting that electrophysiological measurements can indicate both the presence and progression of tauopathic degeneration.
Redox state and cellular uptake of copper is regulated by N-terminus of human Copper Transporter-1
Authors: Kar Sumanta , Sen Samarpita , Maji Saptarshi , Ruturaj  , Paul Rupam , Dutt Sohini , Mondal Basudeb , Rodriguez-Boulan Enrique , Schreiner Ryan , Sengupta Durba , Gupta Arnab
Published: August 2021

Copper(I) is essential for all life forms. Though Cu(II) is most abundant state in environment, its reduction to Cu(I) is prerequisite for bio-utilization, by a mechanism that is uncharacterized. We show that in human Copper Transporter-1, two amino-terminal methionine-histidine clusters and neighbouring aspartates distinctly binds Cu(II) and Cu(I) preceding its import. The endocytosis of hCTR1 from basolateral membrane of polarized epithelia to Common-Recycling-Endosomes is dependent on copper reduction and Cu(I) coordination by methionines. The transient binding of both Cu(II) and Cu(I) during the reduction process facilitated by aspartates acts as another crucial determinant of hCTR1 endocytosis. Mutating7Met-Gly-Met9and Asp13abrogates copper uptake and endocytosis that is correctable by reduced and non-reoxidizable Cu(I). Histidines clusters are crucial for hCTR1 functioning at limiting copper. Finally, we show that two N-terminal His-Met-Asp clusters exhibit functional complementarity in regulating Cu(I)-induced hCTR1 endocytosis. We propose a mechanistic model where His-Met-Asp residues of amino-terminal hCTR1 coordinates copper and maintains its reduced state crucial for uptake.
Structures of full-length glycoprotein hormone receptor signaling complexes
Authors: Duan Jia , Xu Peiyu , Cheng Xi , Mao Chunyou , Croll Tristan , He Xinheng , Shi Jingjing , Luan Xiaodong , Yin Wanchao , You Erli , Liu Qiufeng , Zhang Shuyang , Jiang Hualiang , Zhang Yan , Jiang Yi , Xu H. Eric
Published: August 2021

Luteinizing hormone (LH) and chorionic gonadotropin (CG) are members of the glycoprotein hormone family essential to human reproduction and are important therapeutic drugs. They activate the same G protein-coupled receptor, LHCGR, by binding to the large extracellular domain (ECD). Here we report four cryo-EM structures of LHCGR, two wildtype receptor structures in the inactive and active states, and two constitutively active mutated receptor structures. The active structures are bound to CG and Gs heterotrimer, with one of the structure also containing the allosteric agonist, Org43553. The structures reveal a distinct ‘push and pull” mechanism of receptor activation, in which the ECD is pushed by the bound hormone and pulled by the extended hinge loop next to the transmembrane domain (TMD). A highly conserved 10-residue fragment (P10) from the hinge C-terminal loop at the ECD-TMD interface functions as a tethered agonist to induce conformational changes in TMD and G-protein coupling. Org43553 binds to a TMD pocket and interacts directly with P10 that further stabilizes the receptor in the active conformation. Together, these structures provide a common model for understanding glycoprotein hormone signal transduction and dysfunction, and inspire the search for clinically suitable small molecular compounds to treat endocrine diseases.
Contribution of arm movements to balance recovery after tripping in older adults
Authors: Bruijn Sjoerd M. , Sloot Lizeth H. , Kingma Idsart , Pijnappels Mirjam
Published: August 2021

Falls are common in daily life, often caused by trips and slips and, particularly in older adults, with serious consequences. Although arm movements play an important role in balance control, there is limited research into the role of arm movements during balance recovery after tripping in older adults. We investigated how older adults use their arms to recover from a trip and the difference in the effects of arm movements between fallers (n=5) and non-fallers (n=11).

Sixteen older males and females (69.7±2.3 years) walked along a walkway and were occasionally tripped over suddenly appearing obstacles. We analysed the first trip using a biomechanical model based on full-body kinematics and force-plate data to calculate whole body orientation during the trip and recovery phase. With this model, we simulated the effects of arm movements at foot-obstacle impact and during trip recovery on body orientation.

Apart from an increase in sagittal plane forward body rotation at touchdown in fallers, we found no significant differences between fallers and non-fallers in the effects of arm movements on trip recovery. Like earlier studies in young adults, we found that arm movements during the recovery phase had most favourable effects in the transverse plane: by delaying the transfer of angular momentum of the arms to the body, older adults rotated the tripped side more forward thereby allowing for a larger recovery step. Older adults that are prone to falling might improve their balance recovery after tripping by learning to prolong ongoing arm movements.
St18 specifies globus pallidus projection neuron identity in MGE lineage
Authors: Nunnelly Luke F. , Campbell Melissa , Lee Dylan I. , Gu Guoqiang , Menon Vilas , Au Edmund
Published: August 2021

The medial ganglionic eminence (MGE) is a progenitor domain in the subpallium that produces both locally-projecting interneurons which undergo tangential migration in structures such as the cortex as well as long-range projection neurons that occupy subcortical nuclei. Very little is known about the transcriptional mechanisms specifying the migratory behavior and axonal projection patterns of these two broad classes of MGE-derived neurons. In this study, we identify St18 as a novel transcriptional determinant specifying projection neuron fate in the MGE lineage. St18 is transiently expressed in the MGE subventricular zone (SVZ) and mantle, and we assessed its function using an ES cell-based model of MGE development. Induction of St18 is sufficient to direct ES-derived MGE neurons to adopt a projection neuron-like identity as defined by migration and morphology. Using genetic loss-of-function in mice, we find that St18 is required for the production of globus pallidus pars externa (GPe) prototypic projection neurons. Single cell RNA sequencing revealed that St18 regulates MGE output of specific neuronal populations: in the absence of St18, we observe a large expansion of cortical interneurons at the expense of putative GPe neurons. Through gene expression analysis we identified a downstream effector of St18, Cbx7, which is a component of Polycomb repressor complex 1. We find that Cbx7 is essential for projection neuron-like migration and is not involved in St18-mediated projection neuron-like morphology. Our results characterize a novel transcriptional determinant that directs GPe prototypic projection neuron identity. Further, we identified a downstream target of St18, Cbx7, which regulates only the migratory behavior of long-range projection neurons, suggesting that specific features of MGE projection neuron identity may be governed in a compartmentalized fashion by distinct transcriptional modules downstream of St18.