bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential impact of prostaglandin analogues on agreement of intraocular pressure measurements obtained by Goldmann applanation, rebound, and noncontact tonometry
Authors: Jung Younhea , Suh Hyun , Moon Jung Il
Published: December 2021

Background

To evaluate the effect of topical prostaglandin analogues on agreement of IOP measurements obtained by Goldmann applanation tonometry (GAT), rebound tonometry (RBT), and noncontact tonometry (NCT) in eyes with primary open- angle glaucoma (POAG).

Methods

Intraocular pressure measurements were obtained using GAT, RBT, and NCT in patients with POAG with or without prostaglandin analogues. The agreement between each tonometry was analysed using Bland-Altman analyses in those with or without prostaglandin analogues. The effect of average IOP on IOP differences was also evaluated.

Results

Among a total of 86 subjects included in the study, 44 patients were using prostaglandin analogues. The difference in IOP measured by GAT and RBT was marginally greater in those with (GAT-RBT: − 0.94 ± 1.63 mmHg) prostaglandin analogues than in those without (− 0.33 ± 1.22 mmHg, P = 0.06). The difference in IOP measured by GAT and NCT was significantly greater in the prostaglandin group (GAT-NCT: 2.40 ± 2.89 mmHg) than in the group without prostaglandin analogues (0.41 ± 1.63 mmHg, P < 0.01). While there was no significant relationship between the average of all tonometries and the difference between tonometries in those without prostaglandin analogues, both RBT and NCT underestimated IOP relative to GAT at higher IOP in those using prostaglandin analogues.

Conclusion

Intraocular pressure measured by RBT and NCT was similar to that measured by GAT in those without prostaglandin analogues. RBT overestimated and NCT underestimated IOP compared to GAT in those using prostaglandin analogues.
Quality of life and asthma control in pregnant women with asthma
Authors: Fazel Nasrin , Kundi Michael , Jensen-Jarolim Erika , Pali-Schöll Isabella Maria , Kazemzadeh Asghar , Esmaily Habibollah , Abdizadeh Mojtaba Fattahi , Akbarzadeh Roya , Ahmadi Raheleh , Jabbari Hossain
Published: December 2021

Background

Asthma is the most commonly occurring respiratory illness during pregnancy. Associations with complications of pregnancy and adverse perinatal outcome have been established. However, little is known about quality of life (QoL) in pregnant women with asthma and how it relates to asthma control particularly for Iran.

Objective

To determine the relationship between asthma related QoL and asthma control and severity.

Methods

We conducted a prospective study in pregnant women with asthma. We used the Asthma Control Questionnaire and the Asthma Quality of Life Questionnaire (AQLQ) and the guidelines of the Global Initiative for Asthma for assessment of asthma severity.

Results

Among 1603 pregnant women, 34 were diagnosed with asthma. Of these 13 had intermittent, 10 mild, 8 moderate and 3 severe persistent asthma. There was a significant decrease of QoL with poorer asthma control (p = 0.014). This decline could be due to limitations of activity in those with poorer asthma control, which is underlined by the significant decline of QoL with increasing asthma severity (p = 0.024).

Conclusion

Although the majority of pregnant women with asthma had a favorable score in AQLQ, reduced QoL was related to increased asthma severity and poor asthma control. This underlines the importance of controlling asthma during pregnancy not only for the prevention of adverse pregnancy outcomes but also for the preservation of QoL.
Trigger videos: a novel application of a tool for surgical faculty development
Authors: Arora Anuj , Hoogenes Jen , Dath Deepak
Published: December 2021

Background

Trigger videos have occasionally been used in medical education; however, their application to surgical faculty development is novel. We assessed participants’ attitudes towards workshops on intraoperative teaching (IOT) that were anchored by trigger videos, and studied whether they could generate discussion-for-learning among surgeons in this workshop setting.

Methods

Surgeons from multiple specialties attended one of six faculty development workshops where IOT trigger videos were shown and discussed during break-out sessions. Participants completed questionnaires to (1) evaluate videos via survey and feedback, and (2) identify adoptable and discardable IOT techniques. Teaching techniques were collated to identify planned IOT changes and survey data and feedback were analyzed.

Results

A total of 135 surgeons identified 292 adoptable and 202 discardable IOT techniques based on trigger videos and discussions, and 94% of participants reported that the trigger videos were useful and encouraged them to discuss and consider new IOT techniques in their own practice.

Conclusions

Participants reported that the trigger videos were useful and motivating. Surgeons critically reflected on IOT during the sessions, identifying numerous adoptable and discardable techniques relevant to their own teaching styles. Trigger videos can be a valuable tool for surgical faculty development and can be tailored to other medical specialties.
Axillary metastasis from occult breast cancer and synchronous contralateral breast cancer initially suspected to be cancer with contralateral axillary metastasis: a case report
Authors: Song Myung Won , Ki So Yeon , Lim Hyo Soon , Lee Hyo-jae , Lee Ji Shin , Yoon Jung Han
Published: December 2021

Background

Initial detection of axillary metastasis without known ipsilateral breast cancer could be a challenging diagnostic problem. Four options could be considered for the primary site of the malignancy: ipsilateral occult breast cancer, contralateral breast cancer, tumors in other distant organs, and primary axillary malignancy itself. Although breast cancer is known as the most common primary cancer of axillary metastasis, both occult breast cancer and breast cancer with contralateral axillary metastasis (CAM) are rare.

Case presentation

A 63-year-old woman presented with palpable right axillary metastasis, and a tiny contralateral breast cancer was detected by breast magnetic resonance imaging. No lesion was found in the ipsilateral right breast and contralateral left axillary region. Both right axillary metastasis and contralateral breast cancer were positive for estrogen receptor. The diagnostic issue was to determine whether the axillary metastasis was derived from the contralateral breast cancer or not. Right axillary dissection and left breast conserving surgery were performed. The final diagnosis was occult breast cancer that presented with axillary lymph node metastasis and early-stage synchronous contralateral breast cancer, based on clinical evidence and postoperative pathologic results. After surgery, systemic treatment and whole breast irradiation were administered. No recurrence or metastasis was observed 15 months postoperatively.

Conclusion

For accurate diagnosis of axillary metastasis without detectable ipsilateral breast cancer, multifaceted diagnostic approach considering clinical, radiological, and pathological evidences is required.
Clinical application of non-invasive prenatal diagnosis of phenylketonuria based on haplotypes via paired-end molecular tags and weighting algorithm
Authors: Peng Dai , Ganye Zhao , Gege Sun , Yanjie Xia , Ning Liu , Xiangdong Kong
Published: December 2021

Background

Phenylketonuria (PKU) is a metabolic disease that can cause severe and irreversible brain damage without treatment.

Methods

Here we developed a non-invasive prenatal diagnosis (NIPD) technique based on haplotypes via paired-end molecular tags and weighting algorithm and applied it to the NIPD of PKU to evaluate its accuracy and feasibility in the early pregnancy. A custom-designed hybridization probes containing regions in phenylalanine hydroxylase (PAH) gene and its 1 Mb flanking region were used for target sequencing on genomic and maternal plasma DNA (7–13 weeks of gestation) to construct the parental haplotypes and the proband’s haplotype. Fetal haplotype was then inferred combined with the parental haplotypes and the proband’s haplotype. The presence of haplotypes linked to both the maternal and paternal mutant alleles indicated affected fetuses. The fetal genotypes were further validated by invasive prenatal diagnosis in a blinded fashion.

Results

This technique has been successfully applied in twenty-one cases. Six fetuses were diagnosed as patients carrying both of the mutated haplotypes inherited from their parents. Eleven fetuses were carriers of one heterozygous PAH variants, six of which were paternal and five of which were maternal. Four fetuses were absence of pathogenic alleles. All results were consistent with the prenatal diagnosis through amniotic fluid.

Conclusions

The results showed that our new technique applied to the genotyping of fetuses with high risk for PKU achieves an accurate detection at an early stage of pregnancy with low fetal fraction in cell free DNA.
A new method for obtaining bankable and expandable adult-like microglia in mice
Authors: You Min-Jung , Rim Chan , Kang Youn-Jung , Kwon Min-Soo
Published: December 2021

Background

The emerging role of microglia in neurological disorders requires a novel method for obtaining massive amounts of adult microglia. We aim to develop a new method for obtaining bankable and expandable adult-like microglia in mice.

Methods

The head neuroepithelial layer (NEL) that composed of microglial progenitor and neuroepithelial cells at mouse E13.5 was dissected and then cultured or banked. Microglia (MG) isolated from the cultured NEL by magnetic-activated cell sorting system were obtained and named NEL-MG.

Results

The NEL included microglia progenitors that proliferate and ramify over time with neuroepithelial cells as feeder. In functional analysis, NEL-MG exhibited microglial functions, such as phagocytosis (microbeads, amyloid β, synaptosome), migration, and inflammatory response following lipopolysaccharide (LPS) stimulation. NEL was passage cultured and the NEL-MG exhibited a higher expression of microglia signature genes than the neonatal microglia, a widely used in vitro surrogate. Banking or long-term passage culture of NEL did not affect NEL-MG characteristics. Transcriptome analysis revealed that NEL-MG exhibited better conservation of microglia signature genes with a closer fidelity to freshly isolated adult microglia than neonatal microglia. NEL-MG could be re-expandable when they were plated again on neuroepithelial cells.

Conclusions

This new method effectively contributes to obtaining sufficient matured form of microglia (adult-like microglia), even when only a small number of experimental animals are available, leading to a broad application in the field of neuroscience.
Impact of rewarming rate on interleukin-6 levels in patients with shockable cardiac arrest receiving targeted temperature management at 33 °C: the ISOCRATE pilot randomized controlled trial
Authors: Lascarrou Jean-Baptiste , Guichard Elie , Reignier Jean , Le Gouge Amélie , Pouplet Caroline , Martin Stéphanie , Lacherade Jean-Claude , Colin Gwenhael ,   AfterROSC network, Azais M. , Bachoumas K. , Bailly A. , Camous L. , Colin G. , Crosby L. , Fiancette M. , Henry Lagarrigue M. , Lacherade J. C. , Lascarrou J. B. , Lebert C. , Martin Lefevre L. , Pouplet C. , Reignier J. , Seguin A. , Vinatier I. , Yehia A.
Published: December 2021

Purpose

While targeted temperature management (TTM) has been recommended in patients with shockable cardiac arrest (CA) and suggested in patients with non-shockable rhythms, few data exist regarding the impact of the rewarming rate on systemic inflammation. We compared serum levels of the proinflammatory cytokine interleukin-6 (IL6) measured with two rewarming rates after TTM at 33 °C in patients with shockable out-of-hospital cardiac arrest (OHCA).

Methods

ISOCRATE was a single-center randomized controlled trial comparing rewarming at 0.50 °C/h versus 0.25 °C/h in patients coma after shockable OHCA in 2016–2020. The primary outcome was serum IL6 level 24–48 h after reaching 33 °C. Secondary outcomes included the day-90 Cerebral Performance Category (CPC) and the 48-h serum neurofilament light-chain (NF-L) level.

Results

We randomized 50 patients. The median IL6 area-under-the-curve was similar between the two groups (12,389 [7256–37,200] vs. 8859 [6825–18,088] pg/mL h; P = 0.55). No significant difference was noted in proportions of patients with favorable day-90 CPC scores (13/25 patients at 0.25 °C/h (52.0%; 95% CI 31.3–72.2%) and 13/25 patients at 0.50 °C/h (52.0%; 95% CI 31.3–72.2%; P = 0.99)). Median NF-L levels were not significantly different between the 0.25 °C/h and 0.50 °C/h groups (76.0 pg mL, [25.5–3074.0] vs. 192 pg mL, [33.6–4199.0]; P = 0.43; respectively).

Conclusion

In our RCT, rewarming from 33 °C at 0.25 °C/h, compared to 0.50 °C/h, did not decrease the serum IL6 level after shockable CA. Further RCTs are needed to better define the optimal TTM strategy for patients with CA.

Trial registration ClinicalTrials.gov, NCT02555254. Registered September 14, 2015.

Take-Home Message: Rewarming at a rate of 0.25 °C/h, compared to 0.50 °C, did not result in lower serum IL6 levels after achievement of hypothermia at 33 °C in patients who remained comatose after shockable cardiac arrest. No associations were found between the slower rewarming rate and day-90 functional outcomes or mortality.

140-character Tweet: Rewarming at 0.25 °C versus 0.50 °C did not decrease serum IL6 levels after hypothermia at 33 °C in patients comatose after shockable cardiac arrest.
Patient discharge from intensive care: an updated scoping review to identify tools and practices to inform high-quality care
Authors: Plotnikoff Kara M. , Krewulak Karla D. , Hernández Laura , Spence Krista , Foster Nadine , Longmore Shelly , Straus Sharon E. , Niven Daniel J. , Parsons Leigh Jeanna , Stelfox Henry T. , Fiest Kirsten M.
Published: December 2021

Background

Critically ill patients require complex care and experience unique needs during and after their stay in the intensive care unit (ICU). Discharging or transferring a patient from the ICU to a hospital ward or back to community care (under the care of a general practitioner) includes several elements that may shape patient outcomes and overall experiences. The aim of this study was to answer the question: what elements facilitate a successful, high-quality discharge from the ICU?

Methods

This scoping review is an update to a review published in 2015. We searched MEDLINE, EMBASE, CINAHL, and Cochrane databases from 2013-December 3, 2020 including adult, pediatric, and neonatal populations without language restrictions. Data were abstracted using different phases of care framework models, themes, facilitators, and barriers to the ICU discharge process.

Results

We included 314 articles from 11,461 unique citations. Two-hundred and fifty-eight (82.2%) articles were primary research articles, mostly cohort (118/314, 37.6%) or qualitative (51/314, 16.2%) studies. Common discharge themes across all articles included adverse events, readmission, and mortality after discharge (116/314, 36.9%) and patient and family needs and experiences during discharge (112/314, 35.7%). Common discharge facilitators were discharge education for patients and families (82, 26.1%), successful provider-provider communication (77/314, 24.5%), and organizational tools to facilitate discharge (50/314, 15.9%). Barriers to a successful discharge included patient demographic and clinical characteristics (89/314, 22.3%), healthcare provider workload (21/314, 6.7%), and the impact of current discharge practices on flow and performance (49/314, 15.6%). We identified 47 discharge tools that could be used or adapted to facilitate an ICU discharge.

Conclusions

Several factors contribute to a successful ICU discharge, with facilitators and barriers present at the patient and family, health care provider, and organizational level. Successful provider-patient and provider-provider communication, and educating and engaging patients and families about the discharge process were important factors in a successful ICU discharge.
Albumin and fibrinogen kinetics in sepsis: a prospective observational study
Authors: Omiya Keisuke , Sato Hiroaki , Sato Tamaki , Wykes Linda , Hong Mengyin , Hatzakorzian Roupen , Kristof Arnold S. , Schricker Thomas
Published: December 2021

Background

The measurement of circulating substrate concentrations does not provide information about substrate kinetics. It, therefore, remains unclear if a decrease in plasma concentration of albumin, as seen during critical illness, is a consequence of suppressed production in the liver or increased peripheral clearance. In this study, using stable isotope tracer infusions, we measured albumin and fibrinogen kinetics in septic patients and in a control group of non-septic subjects.

Methods

With the approval from the institutional Research Ethics Board and after obtaining written informed consent from patients or their substitute decision maker, mechanically ventilated patients with sepsis and patients scheduled for elective coronary artery bypass grafting were enrolled. Patients in the non-sepsis group were studied on the day before surgery. The stable isotope L-[ring-2H5]phenylalanine was used to measure absolute synthesis rates (ASR) of albumin and fibrinogen. A priming dose of L-[ring-2H5]phenylalanine (4 µmol/kg) was given followed by a six-hour infusion at a rate of 0.15 µmol/kg/min. At baseline and hourly thereafter, blood was drawn to measure isotope enrichments by gas chromatography/mass spectrometry. Very low density lipoprotein apolipoprotein-B 100 isotopic enrichment was used to represent the isotopic enrichment of the phenylalanine precursor pool from which the liver synthesizes proteins. Plasma albumin and fibrinogen concentrations were also measured.

Results

Mean plasma albumin in septic patients was decreased when compared to non-septic patients, while synthesis rates were comparable. Mean plasma fibrinogen and ASR in septic patients was increased when compared to non-septic patients. In non-septic patients, no statistically significant correlation between plasma albumin and ASR was observed but plasma fibrinogen significantly correlated with ASR. In septic patients, plasma albumin and fibrinogen significantly correlated with ASR.

Conclusions

While septic patients showed lower plasma albumin levels than non-septic patients, albumin synthesis was similar in the two groups suggesting that hypoalbuminemia during sepsis was not caused by suppressed hepatic production but a result of enhanced clearance from the circulation. Hyperfibrinogenemia in septic patients was a consequence of increased fibrinogen production.

Trial registration: ClinicalTrials.gov: NCT02865408 (registered on August 12, 2016) and ClinicalTrials.gov: NCT02549443 (registered on September 15, 2015).
Inonotus obliquus polysaccharide ameliorates serum profiling in STZ-induced diabetic mice model
Authors: Xu Tanye , Li Guodao , Wang Xiaobo , Lv Chongning , Tian Yuanyong
Published: December 2021

Background

Diabetes mellitus is a systemic disease mainly caused by the disorder of metabolism, which has become huge threat to human health. Polysaccharides are the main active substance from Inonotus obliquus (I. obliquus) with hypoglycemic effect. This study aims to evaluate the hypoglycemic activity and investigate the molecular mechanism of I. obliquus polysaccharide (IOP) in streptozotocin (STZ)-induced diabetic mice using metabolomics based on UPLC-Q-Exactive-MS method.

Results

The results showed that the oral administration of IOP in high dose (1.2 g/kg) can significantly reduce the blood glucose with 31% reduction comparing with the diabetic model and relieve dyslipidemia in diabetic mice. By UPLC-Q-Exactive-MS method and multivariate statistical analysis, a total of 15 differential metabolites were identified, including 4 up-regulated and 11 down-regulated biomarkers, of which l-tryptophan, l-leucine, uric acid, 12-HETE, arachidonic acid, PC(20:1(11Z)/14:1(9Z)) and SM(d18:0/24:1(15Z)) were exhibited an important variation, as the potential biomarkers in diabetes. Pathway analysis indicated that phenylalanine, tyrosine and tryptophan biosynthesis and arachidonic acid metabolism were prone to interference in diabetes. Moreover, leucine and proline were reversed and phytosphingosine was further reduced in diabetic mice under the intervention of IOP.

Conclusion

IOP has predominant hyperglycemic effect on STZ-induced diabetic mice via ameliorating serum profiling.
Population study of the gut microbiome: associations with diet, lifestyle, and cardiometabolic disease
Authors: Walker Rebecca L. , Vlamakis Hera , Lee Jonathan Wei Jie , Besse Luke A. , Xanthakis Vanessa , Vasan Ramachandran S. , Shaw Stanley Y. , Xavier Ramnik J.
Published: December 2021

Background

The human gut harbors trillions of microbes that play dynamic roles in health. While the microbiome contributes to many cardiometabolic traits by modulating host inflammation and metabolism, there is an incomplete understanding regarding the extent that and mechanisms by which individual microbes impact risk and development of cardiovascular disease (CVD). The Framingham Heart Study (FHS) is a multi-generational observational study following participants over decades to identify risk factors for CVD by correlating genetic and phenotypic factors with clinical outcomes. As a large-scale population-based cohort with extensive clinical phenotyping, FHS provides a rich landscape to explore the relationships between the gut microbiome and cardiometabolic traits.

Methods

We performed 16S rRNA gene sequencing on stool from 1423 participants of the FHS Generation 3, OMNI2, and New Offspring Spouse cohorts. Data processing and taxonomic assignment were performed with the 16S bioBakery workflow using the UPARSE pipeline. We conducted statistical analyses to investigate trends in overall microbiome composition and diversity in relation to disease states and systematically examined taxonomic associations with a variety of clinical traits, disease phenotypes, clinical blood markers, and medications.

Results

We demonstrate that overall microbial diversity decreases with increasing 10-year CVD risk and body mass index measures. We link lifestyle factors, especially diet and exercise, to microbial diversity. Our association analyses reveal both known and unreported microbial associations with CVD and diabetes, related prescription medications, as well as many anthropometric and blood test measurements. In particular, we observe a set of microbial species that demonstrate significant associations with CVD risk, metabolic syndrome, and type 2 diabetes as well as a number of shared associations between microbial species and cardiometabolic subphenotypes.

Conclusions

The identification of significant microbial taxa associated with prevalent CVD and diabetes, as well as risk for developing CVD, adds to increasing evidence that the microbiome may contribute to CVD pathogenesis. Our findings support new hypothesis generation around shared microbe-mediated mechanisms that influence metabolic syndrome, diabetes, and CVD risk. Further investigation of the gut microbiomes of CVD patients in a targeted manner may elucidate microbial mechanisms with diagnostic and therapeutic implications.
Pneumatosis cystoides intestinalis in a trauma patient presenting with pneumoperitoneum: a case report
Authors: Lebby Elliott , Hanna Medhat , Bui Thanh-Lan , Rudd Adam , Lee Whayoung , Houshyar Roozbeh
Published: December 2021

Background

Pneumatosis cystoides intestinalis is a rare and usually benign condition in which multiple thin-walled cysts develop in the submucosa or subserosa of the gastrointestinal tract. While usually asymptomatic, severe cases can result in pneumoperitoneum, which can be managed surgically or medically depending on circumstances. We present a case of a patient with pneumatosis cystoides intestinalis, which presented as pneumoperitoneum following trauma. To our knowledge, there are no other published cases in which a trauma patient with pneumoperitoneum was found to have radiologic evidence of pneumatosis cystoides intestinalis.

Case presentation

We present the case of a 37-year-old Hispanic male admitted to the hospital after being involved in a motorcycle accident. Computed tomography imaging of the abdomen and pelvis with oral and intravenous contrast demonstrated trace pneumoperitoneum, possibly originating from the splenic flexure of the colon without evidence of extravasation of oral contrast. Laparoscopy with conversion to exploratory laparotomy revealed bowel abnormalities at the distal transverse colon and splenic flexure, which were identified as pneumatosis cystoides intestinalis by pathology. There was no evidence of bowel perforation. A panel of abdominal radiologists attended the computed tomography interpretation to note that incidental atraumatic or traumatic rupture of the cysts could have caused the pneumoperitoneum. The patient had an uncomplicated postoperative course and was transferred to another facility per insurance request.

Conclusions

When presenting in the context of trauma, pneumatosis cystoides intestinalis can lead to difficult management decisions. To our knowledge, there are no existing evidence-based guidelines for the scenario of concurrent pneumatosis cystoides intestinalis, blunt abdominal trauma, and pneumoperitoneum in a patient with a benign abdominal exam. This patient’s pneumoperitoneum was likely caused by rupture of preexisting cysts rather than frank bowel perforation. Patients who are asymptomatic, lack signs of clinically worrisome disease, and have a low pretest probability will likely not benefit from surgery and can be medically managed. Thorough discussion between surgeons and radiologists can be helpful when evaluating the clinical significance of a patient’s pneumatosis cystoides intestinalis and aid in the decision to perform surgery.
Microinjection of antisense oligonucleotides into living mouse testis enables lncRNA function study
Authors: Chen Zhaohui , Ling Li , Shi Xiaolian , Li Wu , Zhai Huicong , Kang Zhenlong , Zheng Bangjin , Zhu Jiaqi , Ye Suni , Wang Hao , Tong Lingxiu , Ni Juan , Huang Chaoyang , Li Yang , Zheng Ke
Published: December 2021

Background

Long non-coding RNAs (lncRNAs) have been the focus of ongoing research in a diversity of cellular processes. LncRNAs are abundant in mammalian testis, but their biological function remains poorly known.

Results

Here, we established an antisense oligonucleotides (ASOs)-based targeting approach that can efficiently knock down lncRNA in living mouse testis. We cloned the full-length transcript of lncRNATsx(testis-specific X-linked) and defined its testicular localization pattern. Microinjection of ASOs through seminiferous tubules in vivo significantly lowered theTsxlevels in both nucleus and cytoplasm. This effect lasted no less than 10 days, conducive to the generation and maintenance of phenotype. Importantly, ASOs performed better in depleting the nuclearTsxand sustained longer effect than small interfering RNAs (siRNAs). In addition to the observation of an elevated number of apoptotic germ cells upon ASOs injection, which recapitulates the documented description ofTsxknockout, we also found a specific loss of meiotic spermatocytes despite overall no impact on meiosis and male fertility.

Conclusions

Our study detailed the characterization ofTsxand illustrates ASOs as an advantageous tool to functionally interrogate lncRNAs in spermatogenesis.
Global and regional shock transmission: an Asian perspective
Authors: Shrestha Nagendra , Sato Kiyotaka
Published: December 2021

This paper constructs and uses the global input–output (GIO) table with 35 industries, 29 endogenous countries and 59 exogenous countries, and develops new indices to measure the degree of shock transmission in terms of intermediate goods and value-added embodied in production induced by negative global demand shock to finished goods. After the Global Financial Crisis (GFC) in 2008, China did not experience a large decline in economic growth, even though China’s gross exports fell most severely among Asian countries. In contrast, a sharp decrease in Japanese GDP in 2009 is a consequence of a substantial decline in finished goods exports, especially in the transport equipment industry. In Japan, the shock effect tends to be absorbed in its domestic sector and is not transmitted to other foreign countries. An asymmetric pattern of shock transmission between Japan and other Asian countries can explain why Japan was more affected by GFC than other Asian countries.
Activating biophilic design patterns as a sustainable landscape approach
Authors: Hady Sahar Ismail Mohamed Abdel
Published: December 2021

Biophilic design elements are found around us in many landscape elements while we do not perceive them as biophilic design patterns. By developing our understanding of biophilic design as a phenomenon, we could discover simple ways to utilize landscape elements and transform them into a good biophilic design that might have positive impacts on a user’s health and well-being. Activating existing biophilic elements as an approach to a sustainable landscape has not been studied yet. Therefore, we rather analyse some international case studies in order to understand how biophilic design patterns can be implemented and see their different forms. Later, we will also go through an Egyptian biophilic design pattern case study and implement it to reach a sustainable landscape model. To summarize, the purpose of this study is to present a new sustainable landscape approach by activating biophilic design patterns in order to increase landscape efficiency.
Can we check serum lithium levels less often without compromising patient safety?
Authors: Heald Adrian H. , Holland David , Stedman Michael , Davies Mark , Duff Chris J. , Parfitt Ceri , Green Lewis , Scargill Jonathan , Taylor David , Fryer Anthony A.
Published: December 2021

Background

Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder.

Aims

This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases.

Method

We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history.

Results

For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency.

Conclusion

We propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.
Unique Transcriptomic Changes Underlie Hormonal Interactions During Mammary Histomorphogenesis in Female Pigs
Authors: Trott Josephine F , Schennink Anke , Horigan Katherine C , Lemay Danielle G , Cohen Julia R , Famula Thomas R , Dragon Julie A , Hovey Russell C
Published: December 2021

Successful lactation and the risk for developing breast cancer depend on growth and differentiation of the mammary gland (MG) epithelium that is regulated by ovarian steroids (17β-estradiol [E] and progesterone [P]) and pituitary-derived prolactin (PRL). Given that the MG of pigs share histomorphogenic features present in the normal human breast, we sought to define the transcriptional responses within the MG of pigs following exposure to all combinations of these hormones. Hormone-ablated female pigs were administered combinations of E, medroxyprogesterone 17-acetate (source of P), and either haloperidol (to induce PRL) or 2-bromo-α-ergocryptine. We subsequently monitored phenotypic changes in the MG including mitosis, receptors for E and P (ESR1 and PGR), level of phosphorylated STAT5 (pSTAT5), and the frequency of terminal ductal lobular unit (TDLU) subtypes; these changes were then associated with all transcriptomic changes. Estrogen altered the expression of approximately 20% of all genes that were mostly associated with mitosis, whereas PRL stimulated elements of fatty acid metabolism and an inflammatory response. Several outcomes, including increased pSTAT5, highlighted the ability of E to enhance PRL action. Regression of transcriptomic changes against several MG phenotypes revealed 1669 genes correlated with proliferation, among which 29 were E inducible. Additional gene expression signatures were associated with TDLU formation and the frequency of ESR1 or PGR. These data provide a link between the hormone-regulated genome and phenome of the MG in a species having a complex histoarchitecture like that in the human breast, and highlight an underexplored synergy between the actions of E and PRL during MG development.
What Tears Couples Apart: A Machine Learning Analysis of Union Dissolution in Germany
Authors: Arpino Bruno , Le Moglie Marco , Mencarini Letizia
Published: December 2021

This study contributes to the literature on union dissolution by adopting a machine learning (ML) approach, specifically Random Survival Forests (RSF). We used RSF to analyze data on 2,038 married or cohabiting couples who participated in the German Socio-Economic Panel Survey, and found that RSF had considerably better predictive accuracy than conventional regression models. The man's and the woman's life satisfaction and the woman's percentage of housework were the most important predictors of union dissolution; several other variables (e.g., woman's working hours, being married) also showed substantial predictive power. RSF was able to detect complex patterns of association, and some predictors examined in previous studies showed marginal or null predictive power. Finally, while we found that some personality traits were strongly predictive of union dissolution, no interactions between those traits were evident, possibly reflecting assortative mating by personality traits. From a methodological point of view, the study demonstrates the potential benefits of ML techniques for the analysis of union dissolution and for demographic research in general. Key features of ML include the ability to handle a large number of predictors, the automatic detection of nonlinearities and nonadditivities between predictors and the outcome, generally superior predictive accuracy, and robustness against multicollinearity.
Regulation of retinal amacrine cell generation by miR-216b and Foxn3
Authors: Zhang Huanqing , Zhuang Pei , Welchko Ryan M. , Dai Manhong , Meng Fan , Turner David L.
Published: December 2021

The mammalian retina contains a complex mixture of different types of neurons. We find that microRNA miR-216b is preferentially expressed in postmitotic retinal amacrine cells in the mouse retina, and expression of miR-216a/b and miR-217 in retina depend in part on Ptf1a, a transcription factor required for amacrine cell differentiation. Surprisingly, ectopic expression of miR-216b directed the formation of additional amacrine cells and reduced bipolar neurons in the developing retina. We identify the Foxn3 mRNA as a retinal target of miR-216b by Argonaute PAR-CLIP and reporter analysis. Inhibition of Foxn3, a transcription factor, in the postnatal developing retina by RNAi increased the formation of amacrine cells and reduced bipolar cell formation. Foxn3 disruption by CRISPR in embryonic retinal explants also increased amacrine cell formation, whereas Foxn3 overexpression inhibited amacrine cell formation prior to Ptf1a expression. Co-expression of Foxn3 partially reversed the effects of ectopic miR-216b on retinal cell formation. Our results identify Foxn3 as a novel regulator of interneuron formation in the developing retina and suggest that miR-216b likely regulates Foxn3 and other genes in amacrine cells.
C2CD6 regulates targeting and organization of the CatSper calcium channel complex in sperm flagella
Authors: Yang Fang , Gracia Gervasi Maria , Orta Gerardo , Tourzani Darya A. , De la Vega-Beltrán Jose Luis , Ruthel Gordon , Darszon Alberto , Visconti Pablo E. , Wang P. Jeremy
Published: December 2021

The CatSper cation channel is essential for sperm capacitation and male fertility. The multi-subunit CatSper complexes form highly organized calcium signaling nanodomains on flagellar membranes. Here, we report identification of an uncharacterized protein, C2CD6, as a subunit of the mouse CatSper complex. C2CD6 contains a calcium-dependent, membrane-targeting C2 domain. C2CD6 associates with the CatSper calcium-selective, core-forming subunits. Deficiency of C2CD6 depletes the CatSper nanodomains from the flagellum and results in male sterility. C2CD6-deficient sperm are defective in hyperactivation and fail to fertilize oocytes both in vitro and in vivo. CatSper currents are present but at a significantly lower level in C2CD6-deficient sperm. Transient treatments with either Ca2+ ionophore, starvation, or a combination of both restore the fertilization capacity of C2CD6-deficient sperm. C2CD6 interacts with EFCAB9, a pH-dependent calcium sensor in the CatSper complex. We postulate that C2CD6 facilitates incorporation of the CatSper complex into the flagellar plasma membrane and may function as a calcium sensor. The identification of C2CD6 may enable the long-sought reconstitution of the CatSper ion channel complex in a heterologous system for male contraceptive development.
Generation and timing of graded responses to morphogen gradients
Authors: Carmon Shari , Jonas Felix , Barkai Naama , Schejter Eyal D. , Shilo Ben-Zion
Published: December 2021

Morphogen gradients are known to subdivide a naive cell field into distinct zones of gene expression. Here, we examine whether morphogens can also induce a graded response within such domains. To this end, we explore the role of the Dorsal protein nuclear gradient along the dorsoventral axis in defining the graded pattern of actomyosin constriction that initiates gastrulation in early Drosophila embryos. Two complementary mechanisms for graded accumulation of mRNAs of crucial zygotic Dorsal target genes were identified. First, activation of target-gene expression expands over time from the ventral-most region of high nuclear Dorsal to lateral regions, where the levels are lower, as a result of a Dorsal-dependent activation probability of transcription sites. Thus, sites that are activated earlier will exhibit more mRNA accumulation. Second, once the sites are activated, the rate of RNA Polymerase II loading is also dependent on Dorsal levels. Morphological restrictions require that translation of the graded mRNA be delayed until completion of embryonic cell formation. Such timing is achieved by large introns, which provide a delay in production of the mature mRNAs. Spatio-temporal regulation of key zygotic genes therefore shapes the pattern of gastrulation.
MRI for paediatric flatfoot: is it necessary?
Authors: Bagley Caroline , McIlhone Sean , Singla Nehal , Berkeley Rupert , O’Donnell Paul , Tennant Sally , Saifuddin Asif
Published: December 2021

Objective:

To determine the additional benefit of MRI for children with flatfoot deformity assessed with weight-bearing radiographs in a specialist paediatric orthopaedic unit.

Methods and materials:

Patient cohort was obtained by searching the Radiology Information System for children referred for investigation of flatfoot. All patients with flatfoot on weight-bearing radiographs who had undergone MRI were included. Radiographs were classified by a consultant musculoskeletal radiologist as showing no underlying abnormality, talo-calcaneal coalition, calcaneonavicular coalition, accessory navicular or other abnormality. MRI studies were classified similarly by a different consultant musculoskeletal radiologist blinded to the radiographic findings.

Results:

33 males and 24 females were included (mean age 12.5 years; range 3–18 years). 24 had bilateral abnormality, so 81 feet were assessed. Radiographs showed no specific abnormality (n = 51), talocalcaneal coalition (n = 6), calcaneonavicular coalition (n = 3), os naviculare (n = 12) or other abnormality (n = 9). MRI showed no specific abnormality (n = 40), talocalcaneal coalition (n = 10), calcaneonavicular coalition (n = 5), os naviculare (n = 12) or other abnormality (n = 14). Assuming MRI as the diagnostic gold-standard, additional relevant diagnostic information was identified in 19 (23.5%) cases, while in the 51 cases for which radiographs provided no specific diagnosis MRI confirmed no underlying abnormality in 31 (60.8%).

Conclusion:

MRI is a valuable adjunct to weight-bearing radiography for investigating paediatric flatfoot deformity.

Advances in knowledge:

MRI is of value in the assessment of paediatric flatfoot, additional diagnostic information to radiography being identified in 23.5% cases, while in 60.8% of cases for which radiographs provided no specific diagnosis MRI confirmed no underlying abnormality.
A case report of anaplastic thyroid cancer and papillary thyroid cancer lymph node metastasis: an unusual presentation as an invasive hypopharyngeal mass
Authors: Vishwanath Veena , Gaunt Nichola , Rana Durgesh , St Leger Dominic , Dykes Michael , Ma Weihong , Garcez Kate , Mani Navin
Published: December 2021

Anaplastic thyroid carcinoma is a rare undifferentiated tumour of the thyroid follicular epithelium. It almost always develops from a pre-existing well-differentiated thyroid cancer with a co-existent thyroid malignancy varying from 5 to 17% . The co-existence of papillary thyroid cancer (PTC) with anaplastic thyroid cancer is a rare occurrence in metastases outside the primary thyroid lesion. Traditionally, this has been regarded as an aggressive form of cancer associated with a dismal prognosis. Recently, the focus has shifted to the development of novel therapies based on the availability of comprehensive genomic profiling platforms (CGP) with a rapid turn-around to identify molecular aberrations in tumours which acts as potential therapeutic targets. In the United Kingdom, we report the case of a 60-year-old woman with an unusual presentation of (metastatic) anaplastic thyroid carcinoma and concomitant papillary thyroid cancer metastasis within a contralateral lymph node. This was initially perceived as a left pyriform fossa mass involving and compressing her left hemi-larynx on clinical and radiological examination. Following the identification of BRAF V600E mutation on CGP, she was started on targeted therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib and demonstrated excellent clinical and radiological response following 7 months of treatment. She has subsequently undergone total thyroidectomy alongside with bilateral neck dissection, and is due to start radioactive iodine treatment to reduce the risk of recurrence of disease.
Κινηματική και δυναμική της παραμόρφωσης, με παράλληλη προτυποποίηση της εξέλιξης της περιοχής του όρους Ελικώνα – Στερεά Ελλάδα
Authors: Παπαντωνίου Γεώργιος
Published: December 2021

Η παρούσα διατριβή έχει ως στόχο την κατανόηση της παραμόρφωσης της περιοχής του όρους Ελικώνα, όπου απαντώνται οι γεωτεκτονικές ενότητες του Παρνασσού, της Βοιωτίας – Δυτικής Θεσσαλίας και της Υποπελαγονικής (Ανώτερης Πελαγονικής).Η αποσαφήνιση της στρωματογραφίας των ενοτήτων, σε συνδυασμό με την κατανόηση της γεωδυναμικής εξέλιξης από την ταφροποίηση του ηπειρωτικού περιθωρίου της Γκοντβάνα – Ευρεία Αδρία – στο ανώτερο Πέρμιο μέχρι τη σημερινή εποχή, παράλληλα με την ανάλυση παλαιο-τάσεων των τεκτονικών δομών, βοήθησε στον διαχωρισμό της παραμόρφωσης σε τρείς φάσεις, ήτοι την προ-ορογενετική, την συν-ορογενετική και την μετα-ορογενετική.Κατά την προ-ορογενετική φάση του Παλαιοκαίνου λειτουργούσαν οι συνιζηματογενείς δομές, γενικής διεύθυνσης ΔΒΔ – ΑΝΑ, ενδεχομένως λόγω δεξιόστροφης περιστροφής του Παρνασσού.Κατά την συν-ορογενετική φάση του Ηωκαίνου, μεταξύ των ενοτήτων Παρνασσού και Βοιωτίας – Δυτικής Θεσσαλίας δημιουργήθηκε ένα επωθητικό σύστημα «ράμπας – επιπέδου», με την κύρια συμπιεστική αποκόλληση να τοποθετείται στην βάση του ηφαιστειοϊζηματογενούς σχηματισμού. Στην νότια πλευρά, λόγω διαφορετικής ταχύτητας επώθησης της ενότητας Βοιωτίας – Δυτικής Θεσσαλίας επάνω στον Παρνασσό, σε σχέση με την ταχύτητα επώθησής της επάνω στην Πίνδο δημιουργείται μια οριζόντιας ολίσθησης δεξιόστροφη δομή. Εντός των ενοτήτων η συμπιεστική τεκτονική εκφράζεται από δομές είτε ανάστροφου χαρακτήρα, είτε οριζόντιας ολίσθησης, ενώ παράλληλα, εντός της ενότητας Βοιωτίας – Δυτικής Θεσσαλίας δημιουργείται μια δεύτερη συμπιεστική αποκόλλησηστη βάση του Βοιωτικού φλύσχη.Η μετα-ορογενετική φάση του Πλειόκαινου – Τεταρτογενούς, διαχωρίζεται σε δυο περιόδους με όριο τα 0.7 Ma, με τον εφελκυσμό αρχικά να εντοπίζεται στην ευρύτερη περιοχή της κεντρικής Ελλάδος, ενώ κατόπιν περιορίστηκε στον σύγχρονο Κορινθιακό και Ευβοϊκό κόλπο.Ως αποτέλεσμα παρατηρείται επαναλειτουργία ορισμένων από τις παλαιότερες δομές, με παράλληλη δημιουργία μερικών νέων, με τον εφελκυσμό να προσδιορίζεται για την πρώτη περίοδο σε ΒΒΑ – ΝΝΔ διεύθυνσης, ενώ για την δεύτερη σε Β – Ν.Η ολοκλήρωση της κινηματικής και δυναμικής ανάλυσης της παραμόρφωσης, οδήγησε στην προτυποποίηση τόσο της γεωλογικής δομής, όσο και της εξέλιξης της με την ένταξη των γεωτεκτονικών ενοτήτων στο ευρύτερο γεωδυναμικό πλαίσιο των Ελληνίδων.
Review of recent lung biomarkers of potential harm/effect for tobacco research
Authors: Beattie Erin , Edmiston Jeffery , Makena Patrudu , Mason Elizabeth , McEwan Mike , Prasad Krishna
Published: December 2021

Biomarkers of potential harm (BoPH) are indicators of biological perturbations which may contribute to the pathophysiology of disease. In this review, we critically assessed the published data on lung-related BoPH in human lung disease for potential use in evaluating the effects of tobacco and nicotine products. A Scopus literature search was conducted on lung disease biomarkers used in a clinical setting over the last 10 years. We identified 1171 papers which were further screened using commercial software (Sciome SWIFT-Active Screener) giving 68 publications that met our inclusion criteria (data on the association of the biomarker with cigarette smoking, the impact of smoking cessation on the biomarker, and differences between smokers and non-smokers), the majority of which investigated chronic obstructive pulmonary disease. Several physiological and biochemical measures were identified that are potentially relevant for evaluating the impact of tobacco products on lung health. Promising new candidates included blood biomarkers, such as surfactant protein D (SP-D), soluble receptor for advanced glycation end products (sRAGE), skin autofluorescence (SAF), and imaging techniques. These biomarkers may provide insights into lung disease development and progression; however, all require further research and validation to confirm their role in the context of tobacco and nicotine exposure, their time course of development and ability to measure or predict disease progression.