bluuebunny/crossref_metadata_2025 huggingface dataset:
Triple gallbladder with heterotopic gastric mucosa: a case report
Authors: Ott Leah , O’Neill John , Cameron Danielle , Callahan Michael J. , Grover Amit , Fox Victor L. , Kim Heung Bae , Lillehei Craig , Cuenca Alex G.
Published: January 2022

Background

Triple gallbladder is a rare congenital anomaly of the biliary tract that can be associated with heterotopic tissue. Gallbladder triplication results from the failure of rudimentary bile ducts to regress during embryological development, and can be difficult to distinguish from Todani type II choledochal cysts and biliary duplication cysts.

Case presentation

A 2-year-old patient presented to our institution with intermittent abdominal pain for 1 year. She had elevated transaminases with imaging concerning for a choledochal cyst. After assessment with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography, she was diagnosed with a gallbladder multiplication and a common bile duct stricture. She underwent laparoscopic cholecystectomy, which confirmed the diagnosis of triple gallbladder. One of the three gallbladders demonstrated heterotopic gastric mucosa on final pathology, including at the cystic duct margin. Follow up testing with a technetium 99 m scan demonstrated a subtle focus of increased activity in the right upper abdomen at the expected location of the common bile duct, concerning for the presence of residual gastric mucosa. The patient remains well without abdominal pain.

Conclusions

We describe the first case of heterotopic gastric mucosa in a triple gallbladder in a young patient presenting with chronic abdominal pain. We also demonstrate the safety and feasibility of laparoscopic cholecystectomy in young children with triple gallbladder. Finally, we propose an interdisciplinary approach to the management of common bile duct strictures in the setting of ectopic acid secretion, involving a combination of medical management, endoscopic intervention, and possible salvage laparoscopic Roux-en-Y hepaticojejunostomy.
Pharmacist assessment of drug-gene interactions and drug-induced phenoconversion in major depressive disorder: a case report
Authors: Del Toro-Pagán N. M. , Matos A. , Bardolia C. , Michaud V. , Turgeon J. , Amin N. S.
Published: January 2022

Background

Response to antidepressant therapy is highly variable among individuals. Pharmacogenomic (PGx) testing presents an opportunity to guide drug selection while optimizing therapy outcomes and/or decreasing the risk for toxicity.

Case presentation

A patient with multiple comorbidities, including severe major depressive disorder (MDD), experienced adverse drug events and undesirable response to multiple antidepressant medications (i.e., bupropion, escitalopram, and venlafaxine). A clinical pharmacist assessed significant drug-gene, drug-drug, and drug-drug-gene interactions as well as other clinical factors to provide recommendations for antidepressant therapy optimization.

Conclusion

This case highlights the importance of PGx testing and the key role of pharmacists in identifying and mitigating drug-related problems and optimizing drug therapy in patients with MDD.
Effective management of district-level malaria control and elimination: implementing quality and participative process improvements
Authors: Agins Bruce , Case Peter , Chandramohan Daniel , Chen Ingrid , Chikodzore Rudo , Chitapi Precious , Chung Amanda , Gosling Roly , Gosling Jonathan , Gumbi Matsiliso , Ikeda Daniel , Madinga Munashe , Mnguni Peliwe , Murungu Joseph , Gueye Cara Smith , Tulloch Jim , Viljoen Greyling ,   Leadership and Engagement for improved Accountability and Delivery of Services Framework Development Group, Agins Bruce , Case Peter , Chandramohan Daniel , Chen Ingrid , Chikodzore Rudo , Chitapi Precious , Chung Amanda , Gosling Roly , Gosling Jonathan , Gumbi Matsiliso , Ikeda Daniel , Madinga Munashe , Mnguni Peliwe , Murungu Joseph , Gueye Cara Smith , Tulloch Jim , Viljoen Greyling
Published: January 2022

Although it is widely recognized that strong program management is essential to achieving better health outcomes, this priority is not recognized in malaria programmatic practices. Increased management precision offers the opportunity to improve the effectiveness of malaria interventions, overcoming operational barriers to intervention coverage and accelerating the path to elimination. Here we propose a combined approach involving quality improvement, quality management, and participative process improvement, which we refer to as Combined Quality and Process Improvement (CQPI), to improve upon malaria program management. We draw on evidence from other areas of public health, as well as pilot implementation studies in Eswatini, Namibia and Zimbabwe to support the proposal. Summaries of the methodological approaches employed in the pilot studies, overview of activities and an outline of lessons learned from the implementation of CQPI are provided. Our findings suggest that a malaria management strategy that prioritizes quality and participative process improvements at the district-level can strengthen teamwork and communication while enabling the empowerment of subnational staff to solve service delivery challenges. Despite the promise of CQPI, however, policy makers and donors are not aware of its potential. Investments are therefore needed to allow CQPI to come to fruition.
Estimating life expectancy adjusted by self-rated health status in the United States: national health interview survey linked to the mortality
Authors: Cho Hyunsoon , Wang Zhuoqiao , Yabroff K. Robin , Liu Benmei , McNeel Timothy , Feuer Eric J. , Mariotto Angela B.
Published: January 2022

Background

Life expectancy is increasingly incorporated in evidence-based screening and treatment guidelines to facilitate patient-centered clinical decision-making. However, life expectancy estimates from standard life tables do not account for health status, an important prognostic factor for premature death. This study aims to address this research gap and develop life tables incorporating the health status of adults in the United States.

Methods

Data from the National Health Interview Survey (1986–2004) linked to mortality follow-up through to 2006 (age ≥ 40, n = 729,531) were used to develop life tables. The impact of self-rated health (excellent, very good, good, fair, poor) on survival was quantified in 5-year age groups, incorporating complex survey design and weights. Life expectancies were estimated by extrapolating the modeled survival probabilities.

Results

Life expectancies incorporating health status differed substantially from standard US life tables and by health status. Poor self-rated health more significantly affected the survival of younger compared to older individuals, resulting in substantial decreases in life expectancy. At age 40 years, hazards of dying for white men who reported poor vs. excellent health was 8.5 (95% CI: 7.0,10.3) times greater, resulting in a 23-year difference in life expectancy (poor vs. excellent: 22 vs. 45), while at age 80 years, the hazards ratio was 2.4 (95% CI: 2.1, 2.8) and life expectancy difference was 5 years (5 vs. 10). Relative to the US general population, life expectancies of adults (age < 65) with poor health were approximately 5–15 years shorter.

Conclusions

Considerable shortage in life expectancy due to poor self-rated health existed. The life table developed can be helpful by including a patient perspective on their health and be used in conjunction with other predictive models in clinical decision making, particularly for younger adults in poor health, for whom life tables including comorbid conditions are limited.
Access to denture restoration services under removable dentures subsidy program for adults aged 65 years and older in Taiwan- an interpretive approach
Authors: Chu Kuan-Yu
Published: January 2022

Background

Access is an important issue in health equality. Availability of dental services and cost subsidies is an important factor affecting access to denture restoration for the elderly. This study aims to explore access to denture restoration services in the elderly removable denture’s subsidy program of  Taiwan.

Methods

Access to the elderly removable dentures subsidy program was measured from two aspects, that is, availability of subsidies and payment for these services and the characteristics of patients and their treatment needs. The first aspect included reimbursements and the number and location of subsidy clinics, and the second aspect included the age and gender distribution of patients and denture types. Information on reimbursement regulations and the number and location of dental clinics providing subsidized services were obtained from the website of the Taoyuan City Public Health Bureau, Taoyuan Hospital, Department of Statistics and Ministry of Health and Welfare. Data on patient characteristics and denture type were obtained through a retrospective survey. We selected individuals who participated in the elderly removable denture’s subsidy program from 2015 to 2018 at the Geriatric Dentistry Department of Taoyuan Hospital. We conducted data analysis using an interpretive approach.

Results

This study found that reimbursement amounts are inadequate, and the availability of subsidized services is low. Moreover, the proportion of male applications is slightly higher than that of females. In addition, among the applicants, removable partial dentures for single or two arches are the most common.

Conclusions

Problems of insufficient numbers of contracted hospitals and low reimbursement amounts are observed in the subsidy program, which are the key factors affecting access to denture restoration services among the elderly. Policymakers should exclude wealthy individuals and offer subsidy only to low-income elderly individuals with missing teeth who are in dire need of financial support to improve their dental health.
Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients
Authors: Sun Zhonghan , Song Zhi-Gang , Liu Chenglin , Tan Shishang , Lin Shuchun , Zhu Jiajun , Dai Fa-Hui , Gao Jian , She Jia-Lei , Mei Zhendong , Lou Tao , Zheng Jiao-Jiao , Liu Yi , He Jiang , Zheng Yuanting , Ding Chen , Qian Feng , Zheng Yan , Chen Yan-Mei
Published: January 2022

Background

COVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology.

Methods

To better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients.

Results

Altered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients.

Conclusions

Our results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.
Strainline: full-length de novo viral haplotype reconstruction from noisy long reads
Authors: Luo Xiao , Kang Xiongbin , Schönhuth Alexander
Published: January 2022

Haplotype-resolved de novo assembly of highly diverse virus genomes is critical in prevention, control and treatment of viral diseases. Current methods either can handle only relatively accurate short read data, or collapse haplotype-specific variations into consensus sequence. Here, we present Strainline, a novel approach to assemble viral haplotypes from noisy long reads without a reference genome. Strainline is the first approach to provide strain-resolved, full-length de novo assemblies of viral quasispecies from noisy third-generation sequencing data. Benchmarking on simulated and real datasets of varying complexity and diversity confirm this novelty and demonstrate the superiority of Strainline.
Striking sex differences in magnetic resonance imaging findings in the sacroiliac joints in the population
Authors: Braun J. , Baraliakos X. , Bülow R. , Schmidt C. O. , Richter A.
Published: January 2022

Background

In patients with axial spondyloarthritis (axSpA), magnetic resonance imaging (MRI) is used to detect bone marrow edema (BME) in sacroiliac joints (SIJ) but SIJ BME are also detected in the population. Not much is known about sex differences in that regard.

Objective

To explore sex-specific differences associated with the extent of BME in the SIJ suggestive of axSpA in a general population cohort study.

Methods

Taking advantage of 793 recently evaluated MRIs of subjects < 45 years taking part in the SHIP cohort, we used negative-binomial (NB) count data regression to analyze factors associated with the extent of SIJ BME. Predictors were explored by model-based boosting (MBB), a machine learning approach.

Results

Estimates of NB regression showed strong effects of sex in interaction with age, BMI, back pain, and particularly HLA-B27. The NB regression model showed incidence rate ratios (IRR) for the main effect of sex (females vs. males): 0.94 [95% CI: 0.63; 1.41], HLA-B27: 4.32 [2.09; 9.8], and for the interaction of sex to HLA-B27: 0.22 [0.06; 0.75]. According to MBB, HLA-B27 positivity, BMI, current smoking, back pain in the last 3 months, the interaction of sex and HLA-B27, and delivery in the last 12 months were of highest importance to explain the extent of SIJ BME.

Conclusions

Different factors were associated with the extent of SIJ BME in females and males. Most importantly, HLA-B27 was relevant only in males but not in females in whom a postpartal state was important. This finding may be relevant for the pathogenesis of axSpA.
Prioritising referrals of individuals at-risk of RA: guidance based on results of a 10-year national primary care observational study
Authors: Garcia-Montoya Leticia , Nam Jacqueline L. , Duquenne Laurence , Villota-Eraso Catalina , Di Matteo Andrea , Hartley Collette , Mankia Kulveer , Emery Paul
Published: January 2022

Background

Musculoskeletal (MSK) symptoms are among the commonest reasons for primary care assessments; however, few individuals will be diagnosed with an inflammatory arthritis (IA) within the following year. The purpose of this study was to investigate, in individuals with new MSK symptoms, the association between patient factors and risk of progression to IA, in order to optimise primary care referrals to rheumatology.

Methods

Individuals ≥16 years old with new non-specific MSK symptoms and no clinical synovitis were recruited by primary care across the UK from July 2007 until May 2019. Those testing positive for the anti-CCP2 assay (anti-CCP+) were invited to Leeds for follow-up. Subjects with a negative result (anti-CCP−) were sent a 1-year questionnaire, and general practitioners were contacted to confirm whether the individual had been diagnosed with an IA by a rheumatologist. Predictors for progression were assessed using multivariable regression analysis.

Results

Six thousand seven hundred eighty individuals were recruited: 3% were anti-CCP+, of whom 45% progressed to IA, predominantly rheumatoid arthritis. Anti-CCP+ participants with high antibody levels had an odds ratio (OR) for progression to IA of 9.42 [P < 0.001, 95% CI (3.13–28.30)], hand pain, OR 2.74 [P = 0.043, 95% CI (1.03–7.27)] and foot pain, OR 4.10 [P = 0.003, 95% CI (1.59–10.54)]. In low-level anti-CCP+ individuals, absence of pain in hands or feet had a negative predictive value of 96% for progression to IA.

One-year follow-up data were available for 5640 anti-CCP− individuals, of whom 53 were diagnosed with IA (0.93%). Pain in hands, OR 2.51 [P = 0.018, 95% CI (1.17–5.39)] or knees, OR 3.03 [P = 0.003, 95% CI (1.47–6.25)] were associated with development of IA within 12 months.

Conclusions

This is the largest prospective primary care study of individuals at risk of IA, and the first one to prospectively investigate the outcome of MSK symptoms in a large anti-CCP− cohort. High anti-CCP levels and pain in hands/feet indicated an increased likelihood of progression to IA. In patients with low anti-CCP level and no pain in the hands/feet, progression is unlikely. In anti-CCP− patients, those with hand or knee pain were at increased risk of progression. This study demonstrates that routinely available tests and joint symptoms provide useful discrimination that may be used to prioritise referrals to rheumatology and avoid a delayed diagnosis.

Trial registration

NCT, NCT02012764. Registered 25 January 2007.
Complaints of daytime sleepiness, insomnia, hypnotic use, and risk of dementia: a prospective cohort study in the elderly
Authors: Cavaillès Clémence , Berr Claudine , Helmer Catherine , Gabelle Audrey , Jaussent Isabelle , Dauvilliers Yves
Published: January 2022

Background

Sleep disturbances are common in elderly and occur frequently in dementia. The impact of excessive daytime sleepiness (EDS), insomnia complaints, sleep quality, and hypnotics on the risk of all-cause dementia, Alzheimer disease (AD), and dementia with vascular component (DVC) remains unclear, as does the association between sleep profile and plasma β-amyloid levels.

Methods

Analyses were carried out on 6851 participants aged 65 years and over randomly recruited from three French cities and free of dementia at baseline. A structured interview and self-questionnaire assessed sleep complaints (EDS, insomnia complaints, sleep quality) and medications at baseline. Incident cases of dementia were diagnosed systematically over a 12-year period. Multivariate Cox models were used to estimate the risk of dementia associated with the sleep complaints considered individually and globally. Plasma β-amyloid levels were measured by an xMAP-based assay technology in 984 subjects.

Results

After adjustment for socio-demographic characteristics, lifestyle, APOE-ε4, cardiovascular factors, and depressive status, EDS had a higher risk of all-cause dementia (HR = 1.21; 95%CI = [1.01–1.46]) and DVC (HR = 1.58; 95%CI = [1.07–2.32]) but not AD. Persistent use of hypnotics increased the risk for all-cause dementia, specifically AD (HR = 1.28; 95%CI = [1.04–1.58]), but not DVC. No association was found for insomnia complaints and sleep quality taken as individual factors or combined with EDS on the risk of dementia. No association was found between β-amyloid, sleep complaints, and incident dementia.

Conclusions

The results suggest a deleterious role of EDS and hypnotics on dementia. Further studies are required to elucidate the mechanisms involved in these associations and whether its management can prevent the risk of dementia.
Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion
Authors: Hu Xiaowen , Pan Jiaji , Li Yongfang , Jiang Yixu , Zheng Haoran , Shi Rubing , Zhang Qi , Liu Chang , Tian Hengli , Zhang Zhijun , Tang Yaohui , Yang Guo-Yuan , Wang Yongting
Published: January 2022

Background

Adipose-derived stem cells (ADSCs) and their extracellular vesicles (EVs) have therapeutic potential in ischemic brain injury, but the underlying mechanism is poorly understood. The current study aimed to explore the contribution of miRNAs in ADSC-EVs to the treatment of cerebral ischemia.

Methods

After the intravenous injection of ADSC-EVs, therapeutic efficacy was evaluated by neurobehavioral tests and brain atrophy volume. The polarization of microglia was assessed by immunostaining and qPCR. We further performed miRNA sequencing of ADSC-EVs and analyzed the relationship between the upregulated miRNAs in ADSC-EVs and microglial polarization-related proteins using Ingenuity Pathway Analysis (IPA).

Results

The results showed that ADSC-EVs reduced brain atrophy volume, improved neuromotor and cognitive functions after mouse ischemic stroke. The loss of oligodendrocytes was attenuated after ADSC-EVs injection. The number of blood vessels, as well as newly proliferated endothelial cells in the peri-ischemia area were higher in the ADSC-EVs treated group than that in the PBS group. In addition, ADSC-EVs regulated the polarization of microglia, resulting in increased repair-promoting M2 phenotype and decreased pro-inflammatory M1 phenotype. Finally, STAT1 and PTEN were highlighted as two downstream targets of up-regulated miRNAs in ADSC-EVs among 85 microglia/macrophage polarization related proteins by IPA. The inhibition of STAT1 and PTEN by ADSC-EVs were confirmed in cultured microglia.

Conclusions

In summary, ADSC-EVs reduced ischemic brain injury, which was associated with the regulation of microglial polarization. miRNAs in ADSC-EVs partly contributed to their function in regulating microglial polarization by targeting PTEN and STAT1.
MicroRNA-377-3p inhibits hepatocellular carcinoma growth and metastasis through negative regulation of CPT1C-mediated fatty acid oxidation
Authors: Zhang Ting , Zhang Yanan , Liu Jie , Ma Yan , Ye Qinong , Yan Xinlong , Ding Lihua
Published: January 2022

Background

Altered lipid metabolism is closely related to the occurrence and development of hepatocellular carcinoma (HCC). Carnitine palmitoyltransferase 1C (CPT1C) is a member of CPT1 family and plays a key role in cancer development and progression. However, how microRNAs (miRNAs) regulate CPT1C-mediated fatty acid transport and oxidation remains to be elucidated.

Methods

Oil Red O staining, mitochondrial, and lipid droplets immunofluorescence staining were used to detect the functions of miR-377-3p and CPT1C in fatty acid oxidation. Colocalization of palmitate and mitochondria was performed to investigate the function of miR-377-3p and CPT1C in fatty acid transport into mitochondria. Fatty acid oxidation (FAO) assay was used to detect the function of miR-377-3p and CPT1C in FAO. Cell proliferation, migration and invasion assays and animal experiments were used to evaluate the role of miR-377-3p/CPT1C axis in HCC progression in vitro and in vivo. Immunofluorescence staining was used to identify the clinical significance of miR-377-3p and CPT1C in HCC patients.

Results

MiR-377-3p inhibits CPT1C expression by targeting its 3’-untranslated region. Through repression of CPT1C, miR-377-3p suppresses fatty acid oxidation by preventing fatty acid from entering into mitochondria and decreasing ATP production in HCC cells. Inhibiting fatty acid oxidation abolishes the ability of miR-377-3p/CPT1C axis to regulate HCC proliferation, migration, invasion and metastasis in vitro and in vivo. In HCC patients, CPT1C is significantly upregulated, and miR-377-3p expression and lipid droplets are negatively correlated with CPT1C expression. High expression of miR-377-3p and CPT1C predict better and worse clinical outcomes, respectively.

Conclusions

We uncover the key function and the relevant mechanisms of the miR-377-3p/CPT1C axis in HCC, which might provide a potential target for the treatment of HCC.
Oncological and functional outcomes following treatment of T1a glottic squamous cell carcinoma with transoral laser microsurgery
Authors: Curry Dennis E. , Forner David , Rigby Matthew H. , Trites Jonathan R. , Corsten Martin , Taylor S. Mark
Published: January 2022

Background

Laryngeal cancers of glottic origin comprise a large proportion of head and neck malignancies. Transoral laser microsurgery (TLM) and radiation therapy are mainstays in the treatment of early stage glottic cancer, but debate persists as to which modality is functionally superior. Furthermore, there is a paucity of North American data related to functional and oncological outcomes in T1a glottic cancer. Here, we assessed oncological and functional outcomes of T1a glottic squamous cell carcinoma (SCC) with TLM to supplement evidence from jurisdictions outside North America.

Methods

This study is a retrospective cohort study performed from a prospectively collected tertiary center institutional TLM database. Patients who were diagnosed with T1a glottic SCC and underwent TLM as their primary treatment were included. Functional outcomes were analyzed using the Voice Handicap Index-10 (VHI-10) questionnaire. Ultimate control with TLM only was considered to be those patients with locoregional control with repeat TLM procedures, but without addition of other modalities. Student's t-test was used to test significance and Kaplan–Meier survival analysis was used to assess oncological outcomes.

Results

48 patients met study criteria. The mean follow-up time was 74 months. The 5-year locoregional, ultimate control with TLM only and laryngeal preservation rates were 83.2%, 90.4% and 100%, respectively. The overall survival and disease-specific survival were 87.2% and 100%, respectively. VHI-10 scores were available for 13/48 patients and mean scores improved non-significantly from pre-op (mean: 11.23; range: 2 to 30; median: 10) and post op (mean: 7.92; range: 0 to 18; median: 8) scoring (p-value = 0.15). Sub-stratification of voice data revealed a significant improvement between pre and post-operative scores (mean difference − 10.6, 95% CI: − 0.99 to − 20.21, p-value = 0.035) for patients with abnormal pre-operative scores (VHI > 11).

Conclusion

To our knowledge, the current work represents one of the first North American studies to report both functional and oncologic outcomes for TLM treatment of T1a glottic SCC. The oncologic and functional outcomes presented here add to existing evidence in favor of TLM as a safe and effective primary treatment option for early staged T1a glottic cancer.

Graphical Abstract
Martian moons exploration MMX: sample return mission to Phobos elucidating formation processes of habitable planets
Authors: Kuramoto Kiyoshi , Kawakatsu Yasuhiro , Fujimoto Masaki , Araya Akito , Barucci Maria Antonietta , Genda Hidenori , Hirata Naru , Ikeda Hitoshi , Imamura Takeshi , Helbert Jörn , Kameda Shingo , Kobayashi Masanori , Kusano Hiroki , Lawrence David J. , Matsumoto Koji , Michel Patrick , Miyamoto Hideaki , Morota Tomokatsu , Nakagawa Hiromu , Nakamura Tomoki , Ogawa Kazunori , Otake Hisashi , Ozaki Masanobu , Russell Sara , Sasaki Sho , Sawada Hirotaka , Senshu Hiroki , Tachibana Shogo , Terada Naoki , Ulamec Stephan , Usui Tomohiro , Wada Koji , Watanabe Sei-ichiro , Yokota Shoichiro
Published: January 2022

Martian moons exploration, MMX, is the new sample return mission planned by the Japan Aerospace Exploration Agency (JAXA) targeting the two Martian moons with the scheduled launch in 2024 and return to the Earth in 2029. The major scientific objectives of this mission are to determine the origin of Phobos and Deimos, to elucidate the early Solar System evolution in terms of volatile delivery across the snow line to the terrestrial planets having habitable surface environments, and to explore the evolutionary processes of both moons and Mars surface environment. To achieve these objectives, during a stay in circum-Martian space over about 3 years MMX will collect samples from Phobos along with close-up observations of this inner moon and carry out multiple flybys of Deimos to make comparative observations of this outer moon. Simultaneously, successive observations of the Martian atmosphere will also be made by utilizing the advantage of quasi-equatorial spacecraft orbits along the moons’ orbits.

Graphical Abstract
Quantifying Collision Frequency and Intensity in Rugby Union and Rugby Sevens: A Systematic Review
Authors: Paul Lara , Naughton Mitchell , Jones Ben , Davidow Demi , Patel Amir , Lambert Mike , Hendricks Sharief
Published: January 2022

Background

Collisions in rugby union and sevens have a high injury incidence and burden, and are also associated with player and team performance. Understanding the frequency and intensity of these collisions is therefore important for coaches and practitioners to adequately prepare players for competition. The aim of this review is to synthesise the current literature to provide a summary of the collision frequencies and intensities for rugby union and rugby sevens based on video-based analysis and microtechnology.

Methods

A systematic search using key words was done on four different databases from 1 January 1990 to 1 September 2021 (PubMed, Scopus, SPORTDiscus and Web of Science).

Results

Seventy-three studies were included in the final review, with fifty-eight studies focusing on rugby union, while fifteen studies explored rugby sevens. Of the included studies, four focused on training—three in rugby union and one in sevens, two focused on both training and match-play in rugby union and one in rugby sevens, while the remaining sixty-six studies explored collisions from match-play. The studies included, provincial, national, international, professional, experienced, novice and collegiate players. Most of the studies used video-based analysis (n = 37) to quantify collisions. In rugby union, on average a total of 22.0 (19.0–25.0) scrums, 116.2 (62.7–169.7) rucks, and 156.1 (121.2–191.0) tackles occur per match. In sevens, on average 1.8 (1.7–2.0) scrums, 4.8 (0–11.8) rucks and 14.1 (0–32.8) tackles occur per match.

Conclusions

This review showed more studies quantified collisions in matches compared to training. To ensure athletes are adequately prepared for match collision loads, training should be prescribed to meet the match demands. Per minute, rugby sevens players perform more tackles and ball carries into contact than rugby union players and forwards experienced more impacts and tackles than backs. Forwards also perform more very heavy impacts and severe impacts than backs in rugby union. To improve the relationship between matches and training, integrating both video-based analysis and microtechnology is recommended. The frequency and intensity of collisions in training and matches may lead to adaptations for a “collision-fit” player and lend itself to general training principles such as periodisation for optimum collision adaptation.

Trial Registration PROSPERO registration number: CRD42020191112.
Advances in Interventional Therapies for Painful Diabetic Neuropathy: A Systematic Review
Authors: Xu Li , Sun Zhuo , Casserly Elizabeth , Nasr Christian , Cheng Jianguo , Xu Jijun
Published: January 2022

BACKGROUND:

Painful diabetic neuropathy (PDN) is one of the major complications of diabetes mellitus. It is often debilitating and refractory to pharmaceutical therapies. Our goal was to systematically review and evaluate the strength of evidence of interventional management options for PDN and make evidence-based recommendations for clinical practice.

METHODS:

We searched PubMed, Scopus, Google Scholar, and Cochrane Llibrary and systematically reviewed all types of clinical studies on interventional management modalities for PDN.

RESULTS:

We identified and analyzed 10 relevant randomized clinical trials (RCTs), 8 systematic reviews/meta-analyses, and 5 observational studies of interventional modalities for PDN using pain as primary outcome. We assessed the risk of bias in grading of evidence and found that there is moderate to strong evidence to support the use of dorsal column spinal cord stimulation (SCS) in treating PDN in the lower extremities (evidence level: 1B+), while studies investigating its efficacy in the upper extremities are lacking. Evidence exists that acupuncture and injection of botulinum toxin-A provide relief in pain or muscle cramps due to PDN with minimal side effects (2B+/1B+). Similar level of evidence supports surgical decompression of lower limb peripheral nerves in patients with intractable PDN and superimposed nerve compression (2B±/1B+). Evidence for sympathetic blocks or neurolysis and dorsal root ganglion (DRG) stimulation is limited to case series (2C+).

CONCLUSIONS:

Moderate to strong evidence exists to support the use of SCS in managing lower extremity pain in patients who have failed conventional medical management for PDN. Acupuncture or injection of botulinum toxin-A can be considered as an adjunctive therapy for PDN. Surgical decompression of peripheral nerves may be considered in patients with PDN superimposed with nerve compression. High-quality studies are warranted to further evaluate the safety, efficacy, and cost-effectiveness of interventional therapies for PDN.
Maternal Fever Associated With Continuous Spinal Versus Epidural Labor Analgesia: A Single-Center Retrospective Study
Authors: Seiler F. Arran , Scavone Barbara M. , Shahul Sajid , Arnolds David E.
Published: January 2022

BACKGROUND:

Neuraxial labor analgesia is associated with elevations in maternal temperature; the mechanism responsible is unknown. Proposed mechanisms have included infection, altered thermoregulation, and inflammation, potentially triggered by local anesthetics. Studies of the association between neuraxial labor analgesia and maternal fever have focused on epidural analgesia, and there have been no comparisons of the rate of maternal fever between continuous spinal and epidural labor analgesia.

METHODS:

We performed a retrospective study to compare the rate of maternal fever between patients who received continuous spinal versus epidural labor analgesia between June 2012 and March 2020. Each patient who received continuous spinal analgesia was matched to 2 patients who received epidural analgesia and had the same nulliparous status. The primary outcome of our study was the incidence of intrapartum maternal fever, which we defined as any temperature ≥38 °C before delivery and compared between the continuous spinal and epidural groups using Fisher exact test.

RESULTS:

We identified 81 patients who received continuous spinal analgesia and 162 matched controls who received epidural analgesia. Demographic and obstetric characteristics of the patients were similar between groups. While the duration of analgesia did not significantly differ, there was markedly increased bupivacaine consumption in women with epidural analgesia. Eight of 81 (9.9%; 95% confidence interval [CI], 5.1–18.3) women with continuous spinal analgesia developed an intrapartum fever compared to 18 of 162 (11.1%; 95% CI, 7.1–16.9) of women with epidural analgesia (P = .83; Fisher exact test).

CONCLUSIONS:

There was no significant difference in the rate of maternal fever between women with continuous spinal compared to epidural labor analgesia. While the route of administration and dose of bupivacaine differs between epidural and spinal labor analgesia, they are titrated to produce similar levels of neuraxial blockade. Our results are consistent with a model in which epidural related maternal fever is due to altered thermoregulation from a central neuraxial block and argue against a direct effect of bupivacaine or fentanyl, although we cannot rule out a concentration-independent effect of bupivacaine or fentanyl or an inflammatory effect of the catheter itself. These retrospective results highlight the importance of prospective and mechanistic study of neuraxial analgesia–related maternal fever.
Atomic Time and Quantum Literacy
Authors: Bühlmann Vera
Published: January 2022

Michel Serres is well known as a strong advocate of science becoming a way of life. As a contribution to the growing literature seeking to address the Anthropocene, this article develops how we could relate the strong and underlying motif of quantum optics that is at work throughout Serres’s oeuvre, and the implications Serres exposes in terms of a natural philosophy (Bühlmann 2020), through what the author sees as the quantum literacy of a world poetics of the current present. Such a literacy is literacy for which the constitutive relation for theoretical thought—between light, vision, and speculation—turns into an intellectual and yet material and physical power. Such a literacy would be an impersonal kind of literacy, a literacy for which poetics, mathematics, and the sciences are inextricably linked in the domain of what is here called—in distinction to atom time—atomic time.
Design of a robotic zebra finch for experimental studies on developmental song learning
Authors: Araguas Alice , Guellaï Bahia , Gauthier Philippe , Richer Florian , Montone Guglielmo , Chopin Adrien , Derégnaucourt Sébastien
Published: January 2022

Birdsong learning has been consolidated as the model system of choice for exploring the biological substrates of vocal learning. In the zebra finch (Taeniopygia guttata), only males sing and they develop their song during a sensitive period in early life. Different experimental procedures have been used in the laboratory to train a young finch to learn a song. So far, the best method to achieve a faithful imitation is to keep a young bird singly with an adult male. Here, we present the different characteristics of a robotic zebra finch that was developed with the goal to be used as a song tutor. The robot is morphologically similar to a life-sized finch: it can produce movements and sounds contingently to the behaviours of a live bird. We present preliminary results on song imitation, and other possible applications beyond the scope of developmental song learning.
Narcolepsy in Parkinson's disease with insulin resistance
Authors: Chunduri Alisha , Crusio Wim E. , Delprato Anna
Published: January 2022

Background: Parkinson’s disease (PD) is characterized by its progression of motor-related symptoms such as tremors, rigidity, slowness of movement, and difficulty with walking and balance. Comorbid conditions in PD individuals include insulin resistance (IR) and narcolepsy-like sleep patterns. The intersecting sleep symptoms of both conditions include excessive daytime sleepiness, hallucinations, insomnia, and falling into REM sleep more quickly than an average person. Understanding of the biological basis and relationship of these comorbid disorders with PD may help with early detection and intervention strategies to improve quality of life.

Methods: In this study, an integrative genomics and systems biology approach was used to analyze gene expression patterns associated with PD, IR, and narcolepsy in order to identify genes and pathways that may shed light on how these disorders are interrelated. A correlation analysis with known genes associated with these disorders (LRRK2, HLA-DQB1, and HCRT) was used to query microarray data corresponding to brain regions known to be involved in PD and narcolepsy. This includes the hypothalamus, dorsal thalamus, pons, and subcoeruleus nucleus. Risk factor genes for PD, IR, and narcolepsy were also incorporated into the analysis.

Results: The PD and narcolepsy signaling networks are connected through insulin and immune system pathways. Important genes and pathways that link PD, narcolepsy, and IR are CACNA1C, CAMK1D, BHLHE41, HMGB1, and AGE-RAGE.

Conclusions: We have identified the genetic signatures that link PD with its comorbid disorders, narcolepsy and insulin resistance, from the convergence and intersection of dopaminergic, insulin, and immune system related signaling pathways. These findings may aid in the design of early intervention strategies and treatment regimes for non-motor symptoms in PD patients as well as individuals with diabetes and narcolepsy.
Disease burden and adverse pregnancy outcomes due to cardiovascular conditions complicating pregnancy in Sri Lanka: a protocol
Authors: Hettiarachchi Ayesh , Lokunarangoda Niroshan , Agampodi Thilini , Agampodi Suneth
Published: January 2022

Background

Cardiovascular diseases (CVD) are the commonest indirect medical cause of maternal deaths worldwide, both in high-income and low and middle-income countries. To minimize the effects of CVD in pregnancy, proper risk assessment and appropriate referral is required. In Sri Lanka, cardiovascular disease complicating pregnancy is a significant cause of maternal mortality, second only to postpartum hemorrhage. Screening for CVD in pregnancy in Sri Lanka is limited to a routine clinical assessment. Evidence-based guidelines are yet to be developed, and this deficit may have resulted in a substantial underestimation of the CVD burden. This study aims to determine the burden of CVD in early pregnancy and develop a risk prediction model to be used in field pregnancy clinics in Sri Lanka to reduce CVD effects in pregnancy.

Methods

A prospective cohort study was carried out in the Anuradhapura district, Sri Lanka. Following registration to the antenatal care, pregnant women fulfilling the eligibility criteria were invited to attend a special clinic at their relevant Medical Officer of Health (MOH) area. Risk assessment was done through history and a clinical examination, and suspected/probable cases were referred for an echocardiogram by a consultant cardiologist. All the recruited participants in the first trimester were prospectively followed up and screened again between 24–28 weeks of the period of amenorrhoea (POA). Antenatal ward admissions with CVD complicating pregnancy will be extracted, and a telephone interview will be carried out between 6–12 weeks after the expected delivery date to cover postpartum morbidities. 

Discussion

This proposed study will be the largest of its kind carried out in the local setting. The study's findings will be beneficial for policymakers to develop guidelines to reduce maternal cardiovascular disease morbidities and mortalities in Sri Lanka.
Paul Celan Revisited – Contextualising His Poetry in the 21st Century
Authors: Heero Aigi
Published: January 2022

Michael Eskin, Karen Leeder, Marko Pajević, eds., Paul Celan Today. A Companion. Berlin/Boston: Walter de Gruyter, 2021. (Companions to Contemporary German Culture, 10). 376 pages.
Biblical education: An introduction
Authors: Bagrowicz Jerzy
Published: January 2022

The Old and the New Testaments are not only the word of God and a source of wisdom that leads to salvation, but also a mine of knowledge and educational wisdom. One can speak of biblical pedagogy which in a sense is a synthesis of God’s wisdom revealed to the people of Israel and their educational experience which they gained in the centuries of their existence. Both the Old and the New Testaments, in their entirety, are a source of this pedagogy adopted by God with respect to the Chosen People as a whole and as individuals. For the educational practice of Christianity, the basic code of ethical norms contained in the Ten Commandments, i.e. the Decalogue, is of particular importance, applying to all believers. These are the rules of conduct that provide the basis in the formation and education of a new person. One cannot understand the principles of education based on the teachings of Jesus Christ without exploring the educational tradition of Israel and comprehending the pedagogy contained in the Old Testament. Jesus Christ did not reject this tradition. He used it to build on it, revealing its much broader and deeper perspective. The biblical pedagogy continues to be valid also in the conditions of the modern world.
Aplikacja INDXR jako narzędzie udostępniania treści Metryki Koronnej – przykład księgi MK 126 z czasów Stefana Batorego
Authors: Szwedo-Kiełczewska Patrycja
Published: January 2022

Artykuł omawia nowe możliwości udostępniania zawartości ksiąg Metryki Koronnej przy wykorzystaniu aplikacji INDXR. Narzędzie to zostało z powodzeniem implementowane w projektach wykorzystujących różnego typu źródła o charakterze masowym. Pozwala ono w prosty sposób połączyć formę opisową i charakterystykę treści źródła z jego skanami. Odpowiada potrzebom i wymaganiom związanym z udostępnianiem zawartości Metryki Koronnej, którą przybliżały dotąd serie Matricularum Regni Poloniae Summaria czy Sumariusz Metryki Koronnej. Seria nowa. Tekst zawiera pewne propozycje dotyczące struktury informacji źródłowych, bazujące na doświadczeniach związanych z wykorzystaniem aplikacji INDXR w opracowaniu księgi MK 126 z czasów panowania Stefana Batorego.
A Shift in Storytelling: Over the Garden Wall as a Literary Reconstruction of Dante’s Divine Comedy.
Authors: Botero Camacho Manuel , Menchero Guillermo Alonso
Published: January 2022

Literature remains a field that serves TV creators and critics as a model both for influence and comparison. The continuity claimed by Thomas Doherty between the most recent TV narrative form with the serialised novels of Dickens or Wharton is not limited to the form itself but to its content as well. Such is the case of the TV animated miniseries Over the Garden Wall, created by Patrick McHale in 2014, whose combination of Victorian fairy-tale imagery and aesthetics, as well as its reliance on literary allusion incarnates this paradigm. Within its narrative there can be found an array of literary references that range from the classics to children’s fables, as well as allusions to history and to different mythologies; an intertextual character that is featured in TV as much as in literary texts from all eras, binding the two forms together. Among the numerous texts referenced in this tale of tales, however, there is one that stands out: Dante Alighieri’s Divine Comedy. This article scrutinises the relationship between Over the Garden Wall and Dante’s Comedy, understanding the show’s protagonist, Wirt, and his quest as a replication of Dante and his descent through Hell. The main claim is that by doing so, Over the Garden Wall also highlights how Campbell’s narrative paradigm, applicable as it is to forms of media other than literature, evinces the narrative continuity, which exists between TV and the written text.
Constitutional Processes and Democratic Commitment
Authors: Horowitz Donald L.
Published: January 2022

The process of making a new constitution often begins in conditions that are not optimal for careful consideration of the process of constitution making and its objectives. Emphasizing the need for a process that maximizes chances for a democratic outcome, this book makes a case for processes that are inclusive, deliberative, and oriented toward achieving consensus rather than merely negotiated outcomes. The book focuses attention on politicians who participate in creating new constitutions. It discusses methods for selecting them, modes of organizing the deliberating and drafting bodies, their standards of decision making, their ways of connecting to the public, and their use of outside advice—all with a view to enhancing the commitment of the participants after the process concludes. Beginning with an enumeration of unpropitious conditions and ways of mitigating them, the chapters provide illustrations of processes that have been relatively successful and others that have gone astray, drawing on an array of country-focused accounts. The volume also identifies characteristic problems, tradeoffs, and pitfalls that can arise in the course of constitution making. The book aims to provide arguments, evidence, and descriptions that will appeal to a wide audience, ranging from curious non-specialist readers to students, experts, and constitution makers and advisors alike.