bluuebunny/crossref_metadata_2025 huggingface dataset:
Every Dying Patient Should Experience a Peaceful Death
Authors: Martin Tammy , Nolen-Vesterlund Martha , McCauley Roberta
Published: September 2022

Providing appropriate end-of-life care is not only a critical part of palliative care but a basic human right. Nurses are well positioned to perform this role; however, the delivery of end-of-life care is difficult. The purpose of this project was to prepare nurses to meet the challenges associated with end-of-life care and to optimize the opportunity for a peaceful death. The project comprised a mixed-methods design, analyzing a palliative care training program for a quantitative and qualitative impact on practice. Preintervention focus group discussions resulted in 6 primary themes concerning the care of these patients: ethical challenges, cultural/spiritual difficulties, troubling emotional aspects, communication challenges, frustrations, and basic unfamiliarity with end-of-life care. Nurses expressed uncertainties about their role in end-of-life care and how best to manage challenges within their scope of practice. There was a statistically significant increase in testing scores from pretraining to posttraining. Postintervention discussions identified changes within nursing practice expressed through 5 primary themes: enhanced communication, symptom management, improved emotional response, improved understanding of ethical principles, and the trajectory of death. Nurses need to receive education to understand their role within end-of-life care and effectively care for the dying patient when cure is no longer an option.
Calcitonin Gene-Related Peptide, Vascular Endothelial Growth Factor, and Clinical Manifestations in Women With Fibromyalgia
Authors: Rus Alma , López-Sánchez José Alberto , García-Ríos María Carmen , Tapia-Haro Rosa María , Casas-Barragán Antonio , Correa-Rodríguez María , Aguilar-Ferrándiz María Encarnación
Published: September 2022

Background

Fibromyalgia is a complex illness to diagnose and treat, which significantly impairs patients’ quality of life.

Objectives

The study aims were to compare levels of calcitonin gene-related peptide and vascular endothelial growth factor between patients with fibromyalgia and healthy controls and to examine their relationship with the main clinical manifestations of fibromyalgia.

Methods

This case–control study included 42 women diagnosed with fibromyalgia and 22 healthy women. Serum calcitonin gene-related peptide and vascular endothelial growth factor levels were spectrophotometrically analyzed by enzyme-linked immunosorbent assay. Clinical manifestations were assessed by means of self-administered questionnaires, including functional capacity in daily living activities, musculoskeletal pain, fatigue, anxiety, and sleep quality. The predictive value of these parameters in fibromyalgia was determined by receiver operating characteristic curve analysis.

Results

Serum calcitonin gene-related peptide levels significantly increased in the fibromyalgia group in comparison to the control group. However, there were no significant differences in vascular endothelial growth factor levels between patients and controls. No significant correlations were found between calcitonin gene-related peptide and vascular endothelial growth factor and the symptoms analyzed.

Discussion

Serum calcitonin gene-related peptide levels were dysregulated in women with fibromyalgia and may be a reliable parameter to help diagnose this complex syndrome.
Use of Prospective Multiplex Immunohistochemistry to Redefine Tissue Pathways of Diagnostic Core Biopsy of Prostate
Authors: Thomas Teresa , Wedden Sarah , Afzal Naveed , Mikel John , D’Arrigo Corrado
Published: September 2022

The incidence of prostatic cancer in the United Kingdom has increased over 40% in the past 30 years. The majority of these cancers are diagnosed by core biopsy, posing a considerable strain on a service that struggles to recruit sufficient histopathologists. The current methodology for tissue diagnosis has a significant false-negative rate, small false-positive rate, and a proportion of indeterminate diagnoses. Therefore, this area presents an opportunity both to improve diagnostic quality and to reduce the burden on resources. We investigated streamlining tissue pathways by increasing the utilization of readily available resources to reduce the burden on scarce resources and improve the accuracy of diagnosis. This involved applying prospective multiplex immunohistochemistry (IHC) using 4 different markers (CK5, p63, racemase, and Ki-67) and 2 chromogens. We conducted a prospective study using over 8000 cores and 3 consultant histopathologists. The pathologists assessed each core using either conventional stains (hematoxylin and eosin) only or multiplex IHC only. The results of this assessment were later compared with the overall assessment made for the final histologic diagnosis. Results show that IHC alone has a positive predictive value of 98.97% and a negative predictive value of 99.91%, while hematoxylin and eosin alone has a positive predictive value of 94.21% and negative predictive value of 99.07%, demonstrating improved diagnostic accuracy. When assessed against the use of on-demand IHC, prospective IHC improves turn-around-times, reduces indeterminate diagnoses, improves pathologist’s accuracy and efficiency and, in overall terms, is cost-effective. In addition, it is possible to structure these tests within the routine of a diagnostic service with little impact on the overall capacity of the laboratory.
Histopathologic Features of Adrenal Cortical Carcinoma
Authors: Gambella Alessandro , Volante Marco , Papotti Mauro
Published: September 2022

Adrenal cortical carcinoma (ACC) is a rare and aggressive malignancy that poses challenging issues regarding the diagnostic workup. Indeed, no presurgical technique or clinical parameters can reliably distinguish between adrenal cortical adenomas, which are more frequent and have a favorable outcome, and ACC, and the final diagnosis largely relies on histopathologic analysis of the surgical specimen. However, even the pathologic assessment of malignancy in an adrenal cortical lesion is not straightforward and requires a combined evaluation of multiple histopathologic features. Starting from the Weiss score, which was developed in 1984, several histopathologic scoring systems have been designed to tackle the difficulties of ACC diagnosis. Dealing with specific histopathologic variants (eg, Liss-Weiss-Bisceglia scoring system for oncocytic ACC) or patient characteristics (eg, Wieneke index in the pediatric setting), these scores remarkably improved the diagnostic workup of ACC and its subtypes. Nevertheless, cases with misleading features or discordant correlations between pathologic findings and clinical behavior still occur. Owing to multicentric collaborative studies integrating morphologic features with ancillary immunohistochemical markers and molecular analysis, ACC has eventually emerged as a multifaceted, heterogenous malignancy, and, while innovative and promising approaches are currently being tested, the future clinical management of patients with ACC will mainly rely on personalized medicine and target-therapy protocols. At the dawn of the new Fifth World Health Organization classification of endocrine tumors, this review will tackle ACC from the pathologist’s perspective, thus focusing on the main available diagnostic, prognostic, and predictive tissue-tethered features and biomarkers and providing relevant clinical and molecular correlates.
Impact of Cerebellar Injury on Neurodevelopmental Outcomes in Preterm Infants with Cerebral Palsy
Authors: Kim Yoo Jinie , Kim Ee-Kyung , Cheon Jung-Eun , Song Huijin , Bang Moon Suk , Shin Hyung-Ik , Shin Seung Han , Kim Han-Suk
Published: September 2022

Objective

We aimed to analyze brain imaging findings and neurodevelopmental outcomes of preterm infants diagnosed with cerebral palsy (CP).

Design

Brain magnetic resonance imaging (MRI) of preterm infants born between 23 and 32 weeks’ gestation and diagnosed with CP at two years corrected age (CA) were evaluated. Brain lesions were categorized as periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and cerebellar hemorrhage (CBH) and graded by the severity. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 18–24 months CA, and the Korean Ages and Stages Questionnaire (K-ASQ) at 18 and 24 months CA.

Results

CP was found in 38 (6.1%) children among 618 survivors. Cerebellar injury (CI) of high-grade CBH and/or atrophy accounted for 25%. Among patients with supratentorial lesions, those having CI showed significantly lower scores on each K-ASQ domain except gross motor than patients without CI. They also revealed a high proportion of patients below the cut-off value of K-ASQ in language, fine motor, and problem-solving domains (P < 0.05), and lower Bayley-III language composite scores (P = 0.038).

Conclusions

Poor neurodevelopmental outcomes other than motor function were associated with CI. Evaluation of the cerebellum may help predict functional outcomes of patients with CP.
Perceived facilitators and barriers to participation in golf for people with vision impairment: a qualitative study
Authors: Beukes Eldré W. , Hynes Niall , Mann David L. , Hawkes Roger , Jayabalan Prakash , Allen Peter M.
Published: September 2022

Objectives

This study aimed to identify facilitators and barriers to participation in vision impaired (VI) golf.

Design

Semi-structured interviews were conducted with 12 VI golfers, 10 guides, and 5 novices during the British VI Golf Open tournament in August 2021.

Results

Qualitative content analysis identified the benefits, facilitators, and challenges of playing VI golf. The role of guides and future developments of the sport were furthermore identified. The benefits extend beyond those related to health, including personal development and a sense of purpose for players, and of reward for guides. Facilitators were largely organizational and having appropriate support and a guide. The challenges to playing and guiding were practical, financial, and logistical. The need to attract a more diverse range of players, along with a reconsideration of the eligibility criteria were central to the perceived sustainability of VI golf.

Conclusion

These results highlight the practical, financial, and logistical challenges contributing to VI golf activity limitations and participation restrictions. Due to the health, personal, and psychosocial benefits, ways of providing practical, financial, and support networks to facilitate engagement in VI golf should be sought. An evidence-based, sport-specific eligibility system was thought to be critical for the future promotion of VI golf.
Outcomes of Heller Myotomy for Esophageal Achalasia
Authors: Tassi Valentina , Lugaresi Marialuisa , Pilotti Vladimiro , Bassi Francesco , Daddi Niccolò , D’Ovidio Frank , Leiva-Juarez Miguel M. , Mattioli Sandro
Published: September 2022

Objective:

To provide information on long-term outcomes of Heller myotomy for esophageal achalasia with or without an antireflux fundoplication.

Background:

Since the adoption of the Heller myotomy, surgeons have modified the original technique in order to balance the cure of dysphagia and the consequent cardial incontinence.

Methods:

Totally, 470 patients underwent primary Heller myotomy between 1955 and 2020. A long abdominal myotomy (AM) was performed in 83 patients, the Ellis limited transthoracic myotomy (TM) in 30, the laparotomic Heller-Dor (L-HD) in 202, the videolaparoscopic Heller-Dor (VL-HD) in 155. The HD was performed under intraoperative manometric assessment. Starting on 1973 these patients underwent a prospective follow-up program of timed lifelong clinical, radiological, endoscopic evaluations.

Results:

Median follow-up time was 23.06 years [interquantile range (IQR): 15.04–32.06] for AM, 29.22 years (IQR: 13.46–40.17) for TM, 14.85 years (IQR: 11.05–21.56) for L-HD and 7.51 years (IQR: 3.25–9.60) for VL-HD. In AM, relapse of dysphagia occurred in 25/71 (35.21%), in TM in 11/30 (36.66%), in LH-D in 10/201 (4.97%), in VL-HD in 3/155 (1.93%). Erosive-ulcerative esophagitis was diagnosed for AM in 28.16%, for TM in 30%, for L-HD in 8.45%, for VL-HD in 2.58%. Overall, the outcome was satisfactory in 52.11% for AM, 41.9% for TM, 89.05% for L-HD, 96.12% for VL-HD.

Conclusions:

The Dor fundoplication drastically reduces postmyotomy gastroesophageal reflux. The Heller-Dor operation is a competitive option for the cure of esophageal achalasia if this operation is performed according to the rules of surgical physiology learned by means of intraoperative manometry.
Transplantation for Nonresectable Colorectal Liver Metastases: Long-Term Follow-Up of the First Prospective Pilot Study
Authors: Solheim Jon M. , Dueland Svein , Line Pål-Dag , Hagness Morten
Published: September 2022

Objective:

To determine whether liver transplantation (LT) can provide long-term overall survival (OS) in selected patients with nonresectable liver-only colorectal liver metastases (nrCRLM).

Background:

In 2005 the first prospective pilot study on LT for nrCRLM was initiated in Norway. We here report long-term data from this study.

Methods:

Main inclusion criteria were nrCRLM, excised primary tumors, and 6 weeks of chemotherapy. Carcinoembryonic antigen >80 µg/L, progressive disease on chemotherapy, size of largest lesion >5.5 cm, and <2 years from primary tumor resection to LT were previously found to be associated with survival. The sum of these factors constitutes the Oslo Score.

Results:

From 2006 to 2012, 23 patients underwent LT in the study. In February 2022, the actual 5-year and 10-year OS after LT were 43.5% and 26.1%, respectively. All patients alive were observed for more than 10 years (range: 133–168 months). Four patients were alive without signs of cancer and with no evidence for disease of median of 102 months (53–133 months). A fifth patient died of noncancer cause after 164 months with no evidence for disease for 31 months. For patients with Oslo Score of 0 or 1, the 5-year and 10-year actual OS was 75% and 50%, respectively (n=6). For patients with Oslo Score of 2, the 5-year and 10- year actual OS 50% was 33% (n=6). All patients with Oslo score 3 or 4 were deceased 86 months post-LT (n=9).

Conclusion:

LT for nrCRLM can provide long term survival and perhaps cure for selected patients. The OS is excellent compared to oncological treatment options and in line with results from studies on resectable CRLM.
Ergosterol extraction: A comparative of methodologies
Authors: Wilkes Thomas I
Published: September 2022

Ergosterol is a component of the cell membrane of mycorrhizal fungi and is frequently used to quantify their biomass. Arbuscular mycorrhizal (AM) fungi and ectomycorrhizal (ECM) fungi establish a symbiotic relationship with a respective host plant and aid in the acquisition of host required water and nutrient in exchange for photosynthetic carbohydrates. Several methods are currently employed for quantification of ergosterol; however, these utilise a series of potentially hazardous chemicals with a varying degree of exposure times to the user. The present method comparative study aims to ascertain the most reliable method to extract ergosterol whilst limiting hazard exposure to the user. Chloroform, cyclohexane, methanol and methanol hydroxide extraction protocols were applied to a total of 320 samples of root samples and a further 320 growth substrate samples across all protocols. Extractions were analysed via HPLC methodologies. Chromagraphic analysis showed chloroform based extraction procedures produced a consistently higher concentration of ergosterol in both root and growth substrate samples. Methanol hydroxide, without the addition of cyclohexane, produced very low concentration of ergosterol, with a reduction of quantified ergosterol of between 80 and 92% compared to chloroform extractions. Hazard exposure was greatly reduced following chloroform extraction protocol when compared with other extraction procedures.
Trends in Coagulase negative Staphylococci (CoNS), England, 2010-2021
Authors: Paranthaman Karthik , Wilson Allegra , Verlander Neville , Rooney Graeme , Macdonald Neil , Nsonwu Olisaeloka , Hope Russell , Fleming Paul , Hatcher James , Ogundipe Enitan , Ratnaraja Natasha , Wan Yu , Pichon Bruno , Westrop Samantha J , Brown Colin S , Demirjian Alicia
Published: September 2022

Objective To review the epidemiology of Coagulase-negative staphylococci (CoNS) in England over the recent 12-year period. Methods Laboratory confirmed CoNS reported from sterile sites in patients in England to the UK Health Security Agency (UKHSA) between 2010 and 2021 were extracted from the national laboratory database and analysed. Results Overall, 668,857 episodes of CoNS were reported. Unspeciated CoNS accounted for 56% (374,228) of episodes, followed by Staphylococcus epidermidis (26%; 174,050), S. hominis (6.5%; 43,501) and S. capitis (3.9%; 25,773). Unspeciated CoNS increased by 8.2% (95% CI, 7.1-9.3) annually between 2010 and 2016, then decreased annually by 6.4% (95% CI: -4.8 to -7.9) until 2021. Speciated CoNS increased by 47.6% (95% CI, 44.5-50.9) annually between 2010 and 2016 and increased annually by 8.9% (95% CI: 5.1 to 12.8) until 2021. Antimicrobial susceptibility profiles differed by species. Conclusions Reports of CoNS from normally sterile body sites in patients in England increased between 2010 and 2016 and remained stable between 2017 and 2021. There has been a striking improvement in species-level identification of CoNS in recent years. Monitoring trends in CoNS epidemiology is crucial for development of observational and clinical intervention studies on individual species.
Burden of Human Metapneumovirus-associated pneumonia among children attending a Tertiary Care Hospital, Kathmandu
Authors: Lamichhane Jyoti , Upreti Milan , Nepal Krishus , Upadhyay Bishnu Prasad , Maharjan Urusha , Shrestha Ram Krishna , Chapagain Ram Hari , Banjara Megha Raj , Thapa Shrestha Upendra
Published: September 2022

Background

Acute Respiratory Tract Infection (ARI) is one of the most common causes of mortality and morbidity worldwide. Every year millions of children suffer from viral Respiratory Tract Infections (RTIs) ranging from mild to severe illnesses. Human Metapneumovirus (HMPV) is among the most frequent viruses responsible for RTIs. However, HMPV infections and their severity among children have not been explored yet in Nepal. Therefore, the study aimed to determine the incidence of HMPV among children attending Kanti Children’s Hospital and assess the clinical characteristics of the infections as well as find out the co-infections.

Methods

A hospital-based cross-sectional study was carried out from September 2018 to April 2019. A total of 105 throat swabs were collected from children clinically suspected of ARIs. The collected samples were tested for the presence of HMPV RNA by Multiplex Real-time PCR (RT-PCR) assay.

Results

The incidence of HMPV in children in Kanti Children’s Hospital was found to be 13.3%. The HMPV was more prevalent in the age group less than three years (21.8%) which was found to be statistically significant (p - 0.038). Cough and fever were the most common clinical features present in all children infected with HMPV followed by rhinorrhea, sore throat, and wheezing. HMPV positive children were diagnosed with pneumonia (42.9%), bronchiolitis (28.5%), upper respiratory tract infections (14.3%) and asthma (14.3%). The incidence of HMPV was high in late winter (14.3%) followed by early spring (13.5%).

Conclusion

This study provides the baseline information on HMPV and associated co-infection with other respiratory viruses for differential diagnosis and rational use of antibiotics in clinical management.
Combined therapy of prednisone and mTOR inhibitor sirolimus for treating retroperitoneal fibrosis
Authors: Gao Hui , Liu Shibo , Mai Yuanbang , Wang Yuying , Zhang Xue-wu , Zheng Shufen , Luo Chenghua , Pan Cuiping
Published: September 2022

Retroperitoneal fibrosis (RPF) is a rare autoimmune disease with fibrous tissue growth and inflammation in retroperitoneum, whose development could encase surrounding organs and lead to severe conditions. Its current treatments involve long-term uptake of glucocorticoids (e.g., prednisone) for controlling inflammation; however, side effects are common, triggering search for replacement therapies. Here, we surveyed gene-disease databases and discovered that mTOR displayed significant changes in RPF, which we confirmed by immunohistological staining. Next, we inferred from drug-gene databases that mTOR inhibitor compound sirolimus could affect most biological pathways in RPF. We then designed a combined therapy in which a gradual reduction of prednisone was prescribed with a long-term, stable dosage of sirolimus. We implemented a single-arm clinical trial in RPF patients and assessed the treatment effects at three timepoints (0, 12 weeks and 48 weeks of treatment). By assessing fibrous tissue mass by computed tomography, inflammation markers and kidney functions by lab tests, immune cell types and abundances by flow cytometry, and plasma inflammation-related proteins by Olink proteomics, we revealed that our combined therapy resulted in significant fibrosis remission and an overall regression of the immune system towards healthy states. In addition, no obvious side effects were observed. We concluded that this new therapy had the potential to replace long-term steroid monotherapy for treating RPF.
Modeling vaccine allocation and equity implications of COVID-19 containment strategies
Authors: Nakamoto Ichiro
Published: September 2022

Given the shortage of global COVID-19 vaccines, a critical public concern is whether the strategy of allocation exerts a heterogeneous effect on settings that have imbalanced accessibility. Exacerbated by the mutational characteristics of the pathogen, traits of immunity protection of vaccines, and diversification of human behaviors, the pathway to the full eradication of the COVID-19 pandemic is becoming increasingly complicated and indeterminate. Population-wide evaluation of public interventions remains crucial to evaluate the performance of epidemiology policies. This study employs a mathematical compartmental model combined with the observational data of the United States to examine the potential effect of vaccine allocation on the trajectory of COVID-19 transmission and the elicited equity implications. The outcomes imply that allocation strategies substantially impact the cumulative equilibrium size of a pandemic controlling for confounding factors. Under a framework of a two-dose primary vaccination strategy aiming to curb the total infections for high-accessibility settings (HAS) and low-accessibility settings(LAS), the traits of vaccination, pathogen, and human effort integrally affect the equilibrium of the COVID-19 pandemic in the medium perspective (i.e., up to 5 years). Vaccine allocation increases the healthcare and cost burden for HAS temporarily, in contrast, it reduces the risk of COVID-19 transmission for the LAS. The effects are consistent across a variety of profiles. By enhancing the administration rates of primary doses (i.e., mainly through dose 1 and dose 2), the magnitude of the COVID-19 pandemic decreases contingent on confounding factors. To minimize the magnitude of infection, it is of importance to dynamically monitor the immunity protection of vaccines, the dynamics of virus transmission, and the gap in the human effort.
Modelling the impact of interventions on imported, introduced and indigenous malaria infections in Zanzibar, Tanzania
Authors: Das Aatreyee M. , Hetzel Manuel W. , Yukich Joshua O. , Stuck Logan , Fakih Bakar S. , Al-mafazy Abdul-wahid H. , Ali Abdullah , Chitnis Nakul
Published: September 2022

Malaria cases can be classified as imported, introduced or indigenous cases. The World Health Organization definition of malaria elimination requires an area to demonstrate no new indigenous cases have occurred in the last three years. Here, we present a malaria transmission model that incorporates human mobility and distinguishes between imported, introduced and indigenous cases. We test the impact of several interventions on Zanzibar such as reactive case detection, reactive drug administration, treating infected travellers, and transmission reduction on Zanzibar and mainland Tanzania. We find that the majority of new cases on both major islands of Zanzibar are indigenous cases, despite high case importation rates. Combinations of interventions that increase the number of infections treated through reactive case detection or reactive drug administration can lead to substantial decreases in malaria incidence, but for elimination within the next 40 years, transmission reduction in both Zanzibar and mainland Tanzania is necessary.
Greater working memory and speech perception scores in cochlear implant users predict better subjective quality of life and hearing
Authors: Prince Priyanka , Chen Joseph , Le Trung , Lin Vincent , Dimitrijevic Andrew
Published: September 2022

A common concern in individuals with cochlear implants (CIs) is difficulty following conversations in noisy environments and social settings. The ability to accomplish these listening tasks relies on the individual’s working memory abilities and draws upon limited cognitive resources to accomplish successful listening. For some individuals, allocating too much, can result deficits in speech perception and in long term detriments of quality of life. For this study, 31 CI users and NH controls completed a series of online behavioural tests and quality of life surveys, in order to investigate the relationship between visual and auditory working memory, clinical and behavioural measures of speech perception and quality of life and hearing. Results showed NH individuals were superior on auditory working memory and survey outcomes. In CI users, recall performance on the three working memory span tests declined from visual reading span to auditory listening in quiet and then listening in noise and speech perception was predictably worse when presented with noise maskers. Bilateral users performed better on each task compared to unilateral/HA and unilateral only users and reported better survey outcomes. Correlation analysis revealed that memory recall and speech perception ability were significantly correlated with sections of CIQOL and SSQ surveys along with clinical speech perception scores in CI users. These results confirm that hearing condition can predict working memory and speech perception and that working memory ability and speech perception, in turn, predict quality of life. Importantly, we demonstrate that online testing can be used as a tool to assess hearing, cognition, and quality of life in CI users.
Huntingtin Interacting Protein 1 (HIP1) autoantibodies as a novel potential surrogate marker for Rheumatoid Arthritis: Pilot Study
Authors: Surbhi  , Goel Ayushi , Chaturvedi Ved , Verma Sneha , Rawat Sonia , Ganguly Nirmal Kumar , Mittal Shivani Arora
Published: September 2022

Rheumatoid Arthritis (RA), an autoimmune disease, primarily affects synovial joints but has systemic manifestations upon progression. Considering limited specific diagnostic and prognostic biomarkers, identifying the disease early and monitoring its progression is important. Previous reports have shown that Huntingtin Interacting Protein 1 (HIP1) is over-expressed in rat synoviocytes, and its autoantibodies in sera of some cancers has diagnostic relevance. Here, we explored HIP1 and its autoantibody levels along with Th1/Th2/Th17 cytokines in sera of RA patients for their potential as surrogate markers. Relative level of autoantibodies to HIP1 was detected using an in-house developed ELISA. HIP1 expression was found comparable in RA patients and controls. HIP1 autoantibodies were found significantly raised in RA patients (p=0.002) and were higher in patients with active disease, thereby correlating with disease progression (p=0.042). Elevated Th1 and IL-6 cytokines (p=0.024) were found in a subset of patients with active disease, coinciding with their pro-inflammatory profile. This is the first report demonstrating a humoral immune response against HIP1 in RA patients, correlating with an active disease status. Further studies in a larger cohort are required to validate this as a surrogate marker.

Key Points

⍰

HIP1 autoantibodies are significantly increased in sera of RA patients.

⍰

HIP1 autoantibodies correlate with active disease in RA patients.
Power and sample sizes estimation in clinical trials with treatment switching in intention-to-treat analysis: a simulation study
Authors: Deng Lejun , Hsu Chih-Yuan , Shyr Yu
Published: September 2022

Background

Treatment switching, also called crossover, is common in clinical trials because of ethical concerns or other reasons. When it occurs and the primary objective is to identify treatment effects, the most widely used intention-to-treat analysis may lead to underpowered trials. Therefore, we plan to propose an approach to preview power reductions and to estimate sample sizes required for the desired power when treatment switching occurs in the intention-to-treat analysis.

Methods

We proposed a simulation-based approach and developed an R package to attain the purpose.

Results

We simulated a number of randomized trials incorporating treatment switching and investigated the impact of the relative effectiveness of the experimental treatment to the control, the switching probability, the allocation ratio, and the switching time on power reductions and sample sizes estimation. The switching probability and the switching time are key determinants for significant power decreasing and thus sample sizes surging to maintain the desired power. The sample sizes required in randomized trials absence of treatment switching varied from around three-fourths to one-twelfths of the sample sizes required in randomized trials allowing treatment switching as the probability of switched patients increased. The power reductions and sample sizes increase with the decrease of switching time.

Conclusions

The simulation-based approach not only provides a preview for power declining but also calculates the required sample size to achieve an expected power in the intention-to-treat analysis when treatment switching occurs. It will provide researchers and clinicians with useful information before randomized controlled trials are conducted.
Adverse childhood experiences and their impacts on subsequent depression and cognitive impairment in Chinese adults
Authors: Zhang Tiantian , Kan Lena , Jin Changbo , Shi Wenming
Published: September 2022

Background

Adverse childhood experiences (ACEs) are prevalent and have long lasting effects. This study aimed to explore the associations between ACEs exposure with subsequent depression and cognitive impairment and to assess whether sociodemographic characteristics modify these associations.

Method

A total of 14,484 participants from the China Health and Retirement Longitudinal Study (CHARLS) 2015 and life history survey in 2014 were enrolled. Depression was assessed by the 10-item Center for Epidemiologic Studies Depression scale. Cognitive performance was evaluated by three composite measures: episodic memory, mental intactness and global cognition. A wide range of 12 ACE indicators were measured by a validated questionnaire. Multiple regression models and stratified analysis explore the relationship between accumulated ACEs with subsequent depression and cognitive impairment and potential modifiers.

Results

Compared with individuals without ACEs, those who experienced four or more ACEs have a higher risk of subsequent depression (adjusted odds ratio, aOR=2.65, 95% confidence intervals [CIs]: 2.21-3.16), poorer mental intactness (β= -0.317 [-0.508 to -0.125]) and worse global cognition (β= -0.437 [-0.693 to -0.181]). Trend analyses showed a dose-response association between accumulated ACEs with subsequent depression and cognitive impairment. The modifications of the association by age, sex, educational level and family’s financial status during childhood were not observed.

Conclusion

Our study suggests that higher ACEs exposure increases the risk of subsequent depression and cognitive impairment in Chinese adults regardless of sociodemographic characteristics. The findings provide important implications for mitigating the adverse effects of early-life stress and promoting health in adulthood.
A scenario-guided strategy for the future management of biological invasions
Authors: Roura-Pascual Núria , Saul Wolf-Christian , Pérez-Granados Cristian , Rutting Lucas , Peterson Garry D. , Latombe Guillaume , Essl Franz , Adriaens Tim , Aldridge David C. , Bacher Sven , Bernardo-Madrid Rubén , Brotons Lluís , Diaz François , Gallardo Belinda , Genovesi Piero , Golivets Marina , González-Moreno Pablo , Hall Marcus , Kutlesa Petra , Lenzner Bernd , Liu Chunlong , Pagitz Konrad , Pastor Teresa , Rabitsch Wolfgang , Robertson Peter , Roy Helen E. , Seebens Hanno , Solarz Wojciech , Starfinger Uwe , Tanner Rob , Vilà Montserrat , Leung Brian , Garcia-Lozano Carla , Jeschke Jonathan M.
Published: September 2022

Future dynamics of biological invasions are highly uncertain because they depend on multiple environmental, societal and socio-economic drivers. We adopted a qualitative scenario approach to explore the future of invasive alien species (IAS) in Europe and created an overall strategy for their management that considers different plausible future developments. The scenarios and strategy were developed during two online workshops with a multidisciplinary team of experts. First, we downscaled four global scenarios of biological invasions to the European level. Second, we developed a management strategy structured into 19 goals that cover a broad array of IAS-related topics (i.e. policy, research, public awareness and biosecurity), and provided solutions for achieving these goals considering the European scenarios. Third, we identified four interrelated recommendations around which any long-term strategy for managing IAS in Europe can be structured: (i) a European biosecurity regime, (ii) a dedicated communication strategy, (iii) data standardization and management tools, and (iv) a monitoring and assessment system. Finally, we identified the feasibility of the IAS management strategy, finding strong differences among the four scenarios. High levels of technological development, public environmental awareness, and effectiveness of IAS policies facilitated the implementation of the overall management strategy. Together, our results indicate that it is time for a new management of biological invasions in Europe based on a more integrative perspective across sectors and countries to be better prepared for future challenges.
Environmental determinants of round goby invasion refuges at a river scale: implications for conservation of native biodiversity
Authors: Morissette Olivier , Charette Cristina , Windle Matthew J.S. , Francis Abraham , Drouin Annick , Goldsmit Jesica , Derry Alison M.
Published: September 2022

Introductions of exotic invasive species are a global disturbance for natural habitats. The severity of invasions can greatly vary from local to global scales, as observed in invasion refuges, exhibiting lower-than-expected invasion intensity. In this study, we analyzed the effects of water conductivity and wetland presence on the density of the round goby (Neogobius melanostomus) in a large-scale study (> 1300 sites), spanning a 400 km stretch of the St. Lawrence River (Canada). Our results showed that round goby density was null in sites with water conductivity under 100 µS/cm and increased toward a probable biological optimum at 300 µS/cm. The presence of wetlands appeared to also decrease round goby density along the conductivity continuum. Similarly, fish community diversity was maximal outside of the round goby water conductivity optimum. Hence, low water conductivity (<100 µS/cm), in interaction with the presence of wetlands, can provide a refuge for native aquatic species, establishing a simple risk assessment tool for managers. Our results also highlighted the high value of wetland conservation for conservation of native species biodiversity.
The topological shape of gene expression across the evolution of flowering plants
Authors: Palande Sourabh , Kaste Joshua A.M. , Roberts Miles D. , Abá Kenia Segura , Claucherty Carly , Dacon Jamell , Doko Rei , Jayakody Thilani B. , Jeffery Hannah R. , Kelly Nathan , Manousidaki Andriana , Parks Hannah M , Roggenkamp Emily M , Schumacher Ally M , Yang Jiaxin , Percival Sarah , Pardo Jeremy , Husbands Aman Y , Krishnan Arjun , Montgomery Beronda L , Munch Elizabeth , Thompson Addie M , Rougon-Cardoso Alejandra , Chitwood Daniel H , VanBuren Robert
Published: September 2022

Since they emerged ~125 million years ago, flowering plants have evolved to dominate the terrestrial landscape and survive in the most inhospitable environments on earth. At their core, these adaptations have been shaped by changes in numerous, interconnected pathways and genes that collectively give rise to emergent biological phenomena. Linking gene expression to morphological outcomes remains a grand challenge in biology, and new approaches are needed to begin to address this gap. Here, we implemented topological data analysis (TDA) to summarize the high dimensionality and noisiness of gene expression data using lens functions that delineate plant tissue and stress responses. Using this framework, we created a topological representation of the shape of gene expression across plant evolution, development, and environment for the phylogenetically diverse flowering plants. The TDA-based Mapper graphs form a well-defined gradient of tissues from leaves to seeds, or from healthy to stressed samples, depending on the lens function. This suggests there are distinct and conserved expression patterns across angiosperms that delineate different tissue types or responses to biotic and abiotic stresses. Genes that correlate with the tissue lens function are enriched in central processes such as photosynthetic, growth and development, housekeeping, or stress responses. Together, our results highlight the power of TDA for analyzing complex biological data and reveal a core expression backbone that defines plant form and function.

Significance statement

A grand challenge in biology is to link gene expression to phenotypes across evolution, development, and the environment, but efforts have been hindered by biological complexity and dataset heterogeneity. Here, we implemented topological data analysis across thousands of gene expression datasets in phylogenetically diverse flowering plants. We created a topological representation of gene expression across plants and observed well-defined gradients of tissues from leaves to seeds, or from healthy to environmentally stressed. Using this framework, we identified a core and deeply conserved expression backbone that defines plant form and function, with key patterns that delineate plant tissues, abiotic, and biotic stresses. Our results highlight the power of topological approaches for analyzing complex biological datasets.
Neurostimulation Artifact Removal for Implantable Sensors Improves Signal Clarity and Decoding of Motor Volition
Authors: Earley Eric J. , Berneving Anton , Zbinden Jan , Ortiz-Catalan Max
Published: September 2022

As the demand for prosthetic limbs with reliable and multi-functional control increases, recent advances in myoelectric pattern recognition and implanted sensors have proven considerably advantageous. Additionally, sensory feedback from the prosthesis can be achieved via stimulation of the residual nerves, enabling closed-loop control over the prosthesis. However, this stimulation can cause interfering artifacts in the electromyographic (EMG) signals which deteriorate the reliability and function of the prosthesis. Here, we implement two real-time stimulation artifact removal algorithms, Template Subtraction and ε-Normalized Least Mean Squares, and investigate their performance in offline and real-time myoelectric pattern recognition in two transhumeral amputees implanted with nerve cuff and EMG electrodes. We show that both algorithms are capable of significantly improving signal-to-noise ratio and offline pattern recognition accuracy of artifact-corrupted EMG signals. Furthermore, both algorithms improved real-time decoding of motor intention during active neurostimulation. Although these outcomes are dependent on the user-specific sensor locations and neurostimulation settings, they nonetheless represent progress towards bi-directional neuromusculoskeletal prostheses capable of multifunction control and simultaneous sensory feedback.
A cocktail of rapamycin, acarbose and phenylbutyrate prevents age-related cognitive decline in mice by altering aging pathways
Authors: Jiang Zhou , He Qianpei , Ladiges Warren
Published: September 2022

Aging is a primary risk factor for cognitive dysfunction and exacerbates multiple biological processes in the brain, including but not limited to nutrient sensing dysregulation, insulin sensing dysfunction and histone deacetylation. Therefore, pharmaceutical intervention of aging targeting several distinct but overlapping pathways provides a basis for testing combinations of drugs as a cocktail. A recent study showed that middle-aged mice treated with a drug cocktail of rapamycin, acarbose, and phenylbutyrate for three months had increased resilience to age related cognitive decline. This finding provided the rationale to investigate the comprehensive transcriptomic and molecular changes within the brain of mice that received this cocktail treatment or control substance. Transcriptome profiles were generated through RNA sequencing and pathway analysis was performed by gene set enrichment analysis to evaluate the overall RNA message effect of the drug cocktail. Molecular endpoints representing aging pathways were measured through immunohistochemistry to further validate the attenuation of brain aging in the hippocampus of mice that received the cocktail treatment, each individual drug or controls. Results indicated that biological processes that enhance aging were suppressed, while autophagy was increased in the brains of mice given the drug cocktail. The molecular endpoint assessments indicated that treatment with the drug cocktail was overall more effective than any of the individual drugs for relieving cognitive impairment by targeting multiple aging pathways.
Accelerated ensemble generation for cyclic peptides using a Reservoir-REMD implementation in GROMACS
Authors: Hsueh Shawn C.C. , Aina Adekunle , Plotkin Steven S.
Published: September 2022

Cyclic peptides naturally occur as antibiotics, fungicides, and immunosuppressants, and have been adapted for use as potential therapeutics. Scaffolded cyclic peptide antigens have many protein characteristics such as reduced toxicity, increased stability over linear peptides, and conformational selectivity, but with fewer amino acids than whole proteins. The profile of shapes presented by a cyclic peptide modulates its therapeutic efficacy, and is represented by the ensemble of its sampled conformations. Although some algorithms excel in creating a diverse ensemble of cyclic peptide conformations, they seldom address the entropic contribution of flexible conformations, and they often have significant practical difficulty producing an ensemble with converged and reliable thermodynamic properties. In this study, an accelerated molecular dynamics (MD) method, reservoir replica exchange MD (R-REMD or Res-REMD), was implemented in GROMACS-4.6.7, and benchmarked on three small cyclic peptide model systems: a cyclized segment of Aβ(cyclo-(CGHHQKLVG)), a cyclized furin cleavage site of SARS-CoV-2 spike (cyclo-(CGPRRARSG)), and oxytocin (disulfide bonded CY-IQNCPLG). Additionally, we also benchmarked Res-REMD on Alanine dipeptide and Trpzip2 to demonstrate its validity and efficiency over REMD. Compared to REMD, Res-REMD significantly accelerated the ensemble generation of cyclo-(CGHHQKLVG), but not cyclo-(CGPRRARSG) or oxytocin. This difference is due to the longer auto-correlation time of torsional angles in cyclo-(CGHHQKLVG)vs. the latter two cyclic peptide systems; The randomly seeded reservoir in Res-REMD thus accelerates sampling and convergence. The auto-correlation time of the torsional angles can thus be used to determine whether Res-REMD is preferable to REMD for cyclic peptides. We provide a github page with modified GROMACS source code for running Res-REMD athttps://github.com/PlotkinLab/Reservoir-REMD.
Comparison of Evaluation Metrics of Deep Learning for Imbalanced Imaging Data in Osteoarthritis Studies
Authors: Liu Shen , Roemer Frank , Ge Yong , Bedrick Edward J. , Li Zong-Ming , Guermazi Ali , Kwoh C. Kent , Sun Xiaoxiao
Published: September 2022

Objective

To compare the evaluation metrics for deep learning methods in the imbalanced imaging data in osteoarthritis (OA) studies.

Method

We first divided MOAKS (MRI Osteoarthritis Knee Score) grades into the presence (MOAKS > 0) and absence (MOAKS = 0) categories. Second, a deep-learning model was trained to the sagittal intermediate-weighted (IW) fat-suppressed (FS) knee MRI images with MOAKS readings from the Osteoarthritis Initiative (OAI) study to predict the presence of bone marrow lesions (BMLs). After the deep learning models were trained, we obtained probabilities of the presence of BMLs from MRI images at the sub-region (15 sub-regions), compartment, and whole-knee levels. We compared different evaluation metrics (e.g., receiver operating characteristic (ROC) and precision-recall (PR) curves) of the deep learning model in the testing data with various class ratios (presence of BMLs vs. absence of BMLs) at these three data levels to assess the model’s performance.

Results

We have demonstrated that the commonly used ROC curve is not sufficiently informative when evaluating the performance of deep learning models in the imbalanced data in OA studies.

Conclusion

The class ratios coupled with results of ROC, PR, and Matthews correlation coefficient (MCC) should be reported in OA studies.