bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating adipose‐derived stem cell exosomes as miRNA drug delivery systems for the treatment of bladder cancer
Authors: Liu Tianyao , Li Tianhang , Zheng Yufeng , Xu Xinyan , Sun Rui , Zhan Shoubin , Guo Xu , Zhao Zihan , Zhu Wenjie , Feng Baofu , Wei Fayun , Jiang Ning , Wang Jin , Chen Xi , Fang Feng , Guo Hongqian , Yang Rong
Published: April 2022

Objectives

Exosomes are essential mediators of intercellular communication as they transport proteins and RNAs between cells. Owing to their tumor‐targeting capacity, immune compatibility, low toxicity, and long half‐life, mesenchymal stem cell‐derived exosomes have great potential for the development of novel antitumor strategies. In this context, the role of exosomes produced by adipose‐derived mesenchymal stem cells (ADSCs) for the treatment of bladder cancer (BC) remains unclear. Here, we investigated the use of ADSCs as a source of therapeutic exosomes, as well as their efficacy in delivering the tumor suppressor miR‐138‐5p in BC.

Methods

ADSCs stably expressing miR‐138‐5p were established using Lentivirus infection, and ADSC‐derived miR‐138‐5p exosomes (Exo‐miR‐138‐5p) were isolated from the cell culture medium. The effect of Exo‐miR‐138‐5p on BC cell migration, invasion, and proliferation was evaluated in vitro using wound healing, transwell invasion, and proliferation assays. The in vivo effect of Exo‐miR‐138‐5p was investigated using a subcutaneous xenograft mouse model.

Results

Exo‐miR‐138‐5p prevented the migration, invasion, and proliferation of BC cells in vitro. Moreover, ADSC‐derived exosomes could penetrate tumor tissues and successfully deliver miR‐138‐5p to suppress the growth of xenograft tumors in vivo.

Conclusions

The present results reveal that ADSC‐derived exosomes are an effective delivery vehicle for small molecule drugs in vivo, and exosome‐delivered miR‐138‐5p is a promising therapeutic agent for BC treatment.
Forgotten and unforgiving
Authors: Eng Marvin H. , Fang Hao Kenith
Published: April 2022

Key Points

Evaluating right ventricular function can be performed in multiple ways with multiple modalitis but is not performed in a standardized manner in daily clinical practice.

Right‐ventricular/pulmonary (RV/PA) coupling is a non‐invasive means of measuring right ventricular reserve by calculating the RV strain/PA systolic pressure ratio.

RV/PA coupling independently predicted 1‐year mortality in patients undergoing MitraClip in this single center retrospective study.
Neuro‐Behcet's disease presenting as solitary midbrain lesion with paroxysmal ataxia and dysarthria (PAD) case report
Authors: Sabry Safan Abeer , EL Beltagi Ahmed , El Sotouhy Ahmed , Yagan Lina , Abunaib Mohammed , Adeli Gholam
Published: April 2022

Paroxysmal dysarthria and ataxia (PDA) is a rare neurological manifestation of stereotyped attacks of sudden ataxic symptoms lasts for few seconds to minutes. We report a case of PDA in a 61‐year‐old male with a solitary homogenously enhancing solitary midbrain lesion and positive HLA‐B51 (Allele 2), controlled with lacosamide.
Primary malignant melanoma of the esophagus
Authors: Karapiperis Dimitrios , Vrakas Spyridon , Ignatova Simone , Tribonias George , Franzen Thomas
Published: April 2022

We report a case of primary malignant melanoma of the esophagus.
Erythrodermic flare‐up of psoriasis with COVID‐19 infection: A report of two cases and a comprehensive review of literature focusing on the mutual effect of psoriasis and COVID‐19 on each other along with the special challenges of the pandemic
Authors: Behrangi Elham , Sadeghzadeh‐Bazargan Afsaneh , Salimi Nastaran , Shaka Zoha , Feyz Kazemi Mohammad Hosein , Goodarzi Azadeh
Published: April 2022

The COVID‐19 pandemic has been extra challenging for patients with chronic diseases. Psoriasis is one of the chronic conditions that its treatment mostly relies on immunosuppressants. In this study, we report two cases with a long history of psoriasis that COVID‐19 infection caused them to undergo erythrodermic psoriasis.
Ectopic variceal bleeding from chronic superior mesenteric vein thrombosis after hemorrhagic pancreatitis
Authors: Flynn Kathryn , Chung Kevin , Brooke Thomas , Keung Jonathan
Published: April 2022

Varices are a common cause of gastrointestinal (GI) bleed. When ectopic, there is often a delay in diagnosis as it is difficult to localize these varices. Ectopic small bowel varices usually arise from portal hypertension, which commonly develops in the setting of cirrhosis. This case presents a much rarer cause of bleeding ectopic varices with portal hypertension secondary to chronic superior mesenteric vein (SMV) thrombosis that developed after an episode of hemorrhagic pancreatitis. An 81‐year‐old man with a past medical history of a recent GI bleeds secondary to an arteriovenous malformation presented to the hospital with continued melena after a recent admission at another hospital for the same symptom. Upper endoscopy and colonoscopy showed no evidence of active bleeding. Subsequently computed tomography angiography (CTA) showed bleeding from collaterals in the third part of the duodenum, consistent with ectopic varices. The CTA also showed SMV thrombosis. The patient underwent an ultrasound‐guided transhepatic venogram with coiling and sclerosant embolization of SMV varices and distal SMV balloon angioplasty. Capsule endoscopy after showed no evidence of further bleeding. The patient was discharged 72 h after the intervention with stabilized hemoglobin and resolved melena. Ectopic varices should be on the differential diagnosis for patients presenting with a GI bleed that remains nonlocalized after endoscopy and colonoscopy. EGD or colonoscopy is the first‐line intervention for the treatment of bleeding ectopic varices. If unreachable by these means, percutaneous coil embolization is an alternative way to stabilize the patient. As no general management guidelines exist, treatment of bleeding ectopic varices should continue to be case‐dependent and involve a multidisciplinary team.
A case of retroperitoneal abscess caused by infection of urachal remnant
Authors: Yoneda Akira , Hida Taiji , Tetsuo Hanako , Fukui Saeko , Murakami Shunsuke , Miyoshi Takayuki , Okamoto Tatsuya , Kitasato Amane , Takeshita Hiroaki , Kuroki Tamotsu
Published: April 2022

Infection of urachal remnant may cause recurrent abscesses. In the current case report, we describe a urachal remnant infection leading to a retroperitoneal abscess, which is an extremely rare condition. In such cases, the recommended treatment is urachal remnant resection.
Undiagnosed polycythemia, an uncommon cause of Wallenberg syndrome: A case report
Authors: Rayamajhi Aadesh , Pokhrel Biraj , Khanal Shambhu , Shrestha Anjan
Published: April 2022

A 26‐year‐old man presented with difficulty swallowing, dizziness, hiccups, and Horner's syndrome. Clinical and neuroimaging collaboration confirmed lateral medullary syndrome. Polycythemia was identified as the only attributable risk factor. However, the cause of polycythemia could not be assessed further. Polycythemia was managed with phlebotomy.
Concomitant lymphoplasmacytic lymphoma, multiple myeloma, and amyloidosis: A diagnostic and therapeutic challenge
Authors: Ceballos Candela , Alburquerque Cristina , Zabalza Amaya , Quispe Iván , Panizo Ángel , Burguete Yolanda , Redondo Ana Margarita , Mateos María Carmen
Published: April 2022

We report a case based on simultaneous occurrence of Waldenström macroglobulinemia, myeloma and amyloidosis as a collision neoplasm. The strangeness and severity of the case presented a diagnostic and therapeutic challenge, which required individualised treatment and close follow‐up to achieved stringent complete response.
Cytomorphology of NUTM1‐rearranged sarcoma involving pleural fluid
Authors: Chen Longwen , Larsen Brandon , Dermawan Josephine K. , Zarka Matthew A.
Published: April 2022

We describe an exceedingly rare cytology case of a NUTM1‐rearranged sarcoma involving pleural fluid. A 48‐year‐old female presented with progressive abdominal pain. Computed tomography (CT) scan of the abdomen revealed a 5.6 cm soft tissue mass in the right hemi‐abdomen. Needle core biopsy of the mass showed a small round cell tumor. Extensive work‐up including next generation sequencing (NGS) demonstrated a NUTM1:MXI1 rearranged sarcoma. The patient was first treated with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy. She responded initially and then progressed with multiple masses in the abdomen and pleural effusion. The cytology of the pleural effusion showed clusters and single small round blue cells. Some of them displayed rhabdoid morphology. Immunostains of NUT antibody on cell block demonstrated strong positivity of NUT. NUTM1‐rearranged sarcoma is an emerging class of mesenchymal neoplasm and the cytomorphology of this neoplasm in liquid‐based cytology (LBC) is yet to be described. We herein reported the first cytology case of NUTM1‐rearranged sarcoma in pleural fluid.
Aperiodic electrophysiological activity in preterm infants is linked to subsequent autism risk
Authors: Shuffrey Lauren C. , Pini Nicolò , Potter Mandy , Springer Priscilla , Lucchini Maristella , Rayport Yael , Sania Ayesha , Firestein Morgan , Brink Lucy , Isler Joseph R. , Odendaal Hein , Fifer William P.
Published: April 2022

Approximately 7% of preterm infants receive an autism spectrum disorder (ASD) diagnosis. Yet, there is a significant gap in the literature in identifying prospective markers of neurodevelopmental risk in preterm infants. The present study examined two electroencephalography (EEG) parameters during infancy, absolute EEG power and aperiodic activity of the power spectral density (PSD) slope, in association with subsequent autism risk and cognitive ability in a diverse cohort of children born preterm in South Africa. Participants were 71 preterm infants born between 25 and 36 weeks gestation (34.60 ± 2.34 weeks). EEG was collected during sleep between 39 and 41 weeks postmenstrual age adjusted (40.00 ± 0.42 weeks). The Bayley Scales of Infant Development and Brief Infant Toddler Social Emotional Assessment (BITSEA) were administered at approximately 3 years of age adjusted (34 ± 2.7 months). Aperiodic activity, but not the rhythmic oscillatory activity, at multiple electrode sites was associated with subsequent increased autism risk on the BITSEA at three years of age. No associations were found between the PSD slope or absolute EEG power and cognitive development. Our findings highlight the need to examine potential markers of subsequent autism risk in high‐risk populations other than infants at familial risk.
Interacting lethal and nonlethal human activities shape complex risk tolerance behaviors in a mountain herbivore
Authors: Courbin Nicolas , Garel Mathieu , Marchand Pascal , Duparc Antoine , Debeffe Lucie , Börger Luca , Loison Anne
Published: April 2022

Animals perceive human activities as risky and generally respond with fear‐induced proactive behaviors to buffer the circadian patterns of lethal and nonlethal disturbances, such as diel migrations (DMs) between risky places during safe nighttime and safer places during risky daytime. However, such responses potentially incur costs through movement or reduced foraging time, so individuals should adjust their tolerance when human activities are harmless, through habituation. Yet this is a challenging cognitive task when lethal and nonlethal risks co‐occur, forming complex landscapes of fear. The consequences of this human‐induced complexity have, however, rarely been assessed. We studied the individual DM dynamics of chamois (Rupicapra rupicapra rupicapra), 89 GPS‐tracked individual‐years, from/to trails in the French Alps in areas with co‐occurring lethal (hunting) and nonlethal (hiking and skiing) disturbances, with different intensities across seasons. We developed a conceptual framework relying on the risk‐disturbance hypothesis and habituation to predict tolerance adjustments of chamois under various disturbance contexts and across contrasted seasonal periods. Based on spatial and statistical analyses combining periodograms and multinomial logistic models, we found that DM in relation to distance to a trail was a consistent response by chamois (~85% of individuals) to avoid human disturbance during daytime, especially during the hiking and hunting periods. Such behavior revealed a low tolerance of most chamois to human activities, although there was considerable interindividual heterogeneity in DM. Interestingly, there was an increased tolerance among the most disturbed diel migrants, potentially through habituation, with chamois performing shorter DMs in areas highly disturbed by hikers. Crucially, chamois that were most human‐habituated during the hiking period remained more tolerant in the subsequent harvesting period, which could increase their risk of being harvested. In contrast, individuals less tolerant to hiking performed longer DMs when hunting risk increased, and compared to hiking, hunting exacerbated the threshold distance to trails triggering DMs. No carryover effect of hunting beyond the hunting period was observed. In conclusion, complex human‐induced landscapes of fear with co‐occurring disturbances by nature‐based tourism and hunting may shape unexpected patterns of tolerance to human activities, whereby animal tolerance could become potentially deleterious for individual survival.
Invasive species do not exploit early growing seasons in burned tallgrass prairies
Authors: Ratcliffe Hugh , Ahlering Marissa , Carlson Daren , Vacek Sara , Allstadt Andrew , Dee Laura E.
Published: April 2022

Invasive species management is key to conserving critically threatened native prairie ecosystems. While prescribed burning is widely demonstrated to increase native diversity and suppress invasive species, elucidating the conditions under which burning is most effective remains an ongoing focus of applied prairie ecology research. Understanding how conservation management interacts with climate is increasingly pressing, because climate change is altering weather conditions and seasonal timing around the world. Increasingly early growing seasons due to climate change are shifting the timing and availability of resources and niche space, which may disproportionately advantage invasive species and influence the outcome of burning. We estimated the effects of burning, start time of the growing season, and their interaction on invasive species relative cover and frequency, two metrics for species abundance and dominance. We used 25 observed prairie sites and 853 observations of 267 transects spread throughout Minnesota, USA from 2010 to 2019 to conduct our analysis. Here, we show that burning reduced the abundance of invasive cool‐season grasses, leading to reduced abundance of invasive species as a whole. This reduction persisted over time for invasive cover but quickly waned for their frequency of occurrence. Additionally, and contrary to expectations that early growing season starts benefit invasive species, we found evidence that later growing season starts increased the abundance of some invasive species. However, the effects of burning on plant communities were largely unaltered by the timing of the growing season, although earlier growing season starts weakened the effectiveness of burning on Kentucky bluegrass (Poa pratensis) and smooth brome (Bromus inermis), two of the most dominant invasive species in the region. Our results suggest that prescribed burning will likely continue to be a useful conservation tool in the context of earlier growing season starts, and that changes to growing season timing will not be a primary mechanism driving increased invasion due to climate change in these ecosystems. We propose that future research seek to better understand abiotic controls on invasive species phenology in managed systems and how burning intensity and timing interact with spring conditions.
Revisiting the comparative phylogeography of unglaciated eastern North America: 15 years of patterns and progress
Authors: Lyman Rachel Ann , Edwards Christine E.
Published: April 2022

In a landmark comparative phylogeographic study, “Comparative phylogeography of unglaciated eastern North America,” Soltis et al. (Molecular Ecology, 2006, 15, 4261) identified geographic discontinuities in genetic variation shared across taxa occupying unglaciated eastern North America and proposed several common biogeographical discontinuities related to past climate fluctuations and geographic barriers. Since 2006, researchers have published many phylogeographical studies and achieved many advances in genotyping and analytical techniques; however, it is unknown how this work has changed our understanding of the factors shaping the phylogeography of eastern North American taxa. We analyzed 184 phylogeographical studies of eastern North American taxa published between 2007 and 2019 to evaluate: (1) the taxonomic focus of studies and whether a previously detected taxonomic bias towards studies focused on vertebrates has changed over time, (2) the extent to which studies have adopted genotyping technologies that improve the resolution of genetic groups (i.e., NGS DNA sequencing) and analytical approaches that facilitate hypothesis‐testing (i.e., divergence time estimation and niche modeling), and (3) whether new studies support the hypothesized biogeographic discontinuities proposed by Soltis et al. (Molecular Ecology, 2006, 15, 4261) or instead support new, previously undetected discontinuities. We observed little change in taxonomic focus over time, with studies still biased toward vertebrates. Although many technological and analytical advances became available during the period, uptake was slow and they were employed in only a small proportion of studies. We found variable support for previously identified discontinuities and identified one new recurrent discontinuity. However, the limited resolution and taxonomic breadth of many studies hindered our ability to clarify the most important climatological or geographical factors affecting taxa in the region. Broadening the taxonomic focus to include more non‐vertebrate taxa, employing technologies that improve genetic resolution, and using analytical approaches that improve hypothesis testing are necessary to strengthen our inference of the forces shaping the phylogeography of eastern North America.
Assessing spatiotemporal variation in abundance: A flexible framework accounting for sampling bias with an application to common pochard (Aythya ferina)
Authors: Folliot Benjamin , Caizergues Alain , Tableau Adrien , Souchay Guillaume , Guillemain Matthieu , Champagnon Jocelyn , Calenge Clément
Published: April 2022

Assessing trends in the relative abundance of populations is a key yet complex issue for management and conservation. This is a major aim of many large‐scale censusing schemes such as the International Waterbird Count (IWC). However, owing to the lack of sampling strategy and standardization, such schemes likely suffer from biases due to spatial heterogeneity in sampling effort. Despite huge improvements of the statistical tools that allow tackling these statistical issues (e.g., GLMM, Bayesian inference), many conservationists still prefer to rely on stand‐alone turn‐key statistical tools, often violating the prerequisites put forward by the developers of these tools. Here, we propose a straightforward and flexible approach to tackle the typical statistical issues one can encounter when analyzing count data of monitoring schemes such as the IWC. We rely on IWC counts of the declining common pochard populations of the Northwest European flyway as a case study (period 2002–2012). To standardize the size of sampling units and mitigate spatial autocorrelation, we grouped sampling sites using a 75 × 75 km grid cells overlaid over the flyway of interest. Then, we used a hierarchical modeling approach, assessing population trends with random effects at two spatial scales (grid cells, and sites within grid cells) in order to derive spatialized values and to compute the average population trend at the whole flyway scale. Our approach allowed to tackle many statistical issues inherent to this type of analysis but often neglected, including spatial autocorrelation. Concerning the case study, our main findings are that: (1) the northwestern population of common pochards experienced a steep decline (4.9% per year over the 2002–2012 period); (2) the decline was more pronounced at high than low latitude (11.6% and 0.5% per year at 60° and 46° of latitude, respectively); and, (3) the decline was independent of the initial number of individuals in a given site (random across sites). Beyond the case study of the common pochard, our study provides a conceptual statistical framework for estimating and assessing potential drivers of population trends at various spatial scales.
Distinct mtDNA lineages in free‐ranging Ammotragus(aoudad) from the United States indicate multiple introductions from northern Africa
Authors: Wright Emily A. , Wiedmeier Rachael C. , Roberts Emma K. , Pipkin David R. , Hernández Froylán , Bayouth Joseph P. , Conway Warren C. , Bradley Robert D.
Published: April 2022

Translocation records indicate aoudad (Ammotragus lervia) populations in the United States are a product of multiple human‐mediated introductions. Two mitochondrial markers (cytochrome b, cytb; displacement loop, D loop) and one nuclear gene (prion protein gene exon 3, PRNP) were used to determine: (1) genetic variation, (2) if genetic units correspond to taxonomic designations, (3) the number and geographic origin of translocations, and (4) divergence times. Three phylogenetic analyses (Bayesian inference, maximum likelihood, and parsimony) produced similar topologies with two clades (I and II). Clade I contained progeny of individuals resulting from introductions to Texas and Spain, and individuals from Algeria. Individuals in Clade II were progeny of past introductions to the United States and Europe, and northern Algeria. Clade II was subdivided into two subclades (A and B) representing two haplogroups. No genetic variation was detected in the PRNP sequences. Three haplogroups appeared to correspond to the subspecies A. l. lervia and A. l. sahariensis whose native distribution includes northwestern Africa. Network analyses assigned haplogroups to two major groups similar to those depicted in the phylogenetic analyses. Genetic distances ranged from 0.80% to 5.17% and 2.99% to 15.42% for cytb and D loop, respectively; and were higher than normally recovered for caprids, warranting a reexamination of subspecific status. Divergence dates indicated a major split between A. l. lervia and A. l. sahariensis circa 2.38 mya. Together, the high level of genetic divergences among US populations and apparent presence of two subspecies of aoudad in the United States support the hypothesis of multiple introductions from multiple sources.
Impact of diabetes on COVID‐19 mortality and hospital outcomes from a global perspective: An umbrella systematic review and meta‐analysis
Authors: Kastora Stavroula , Patel Manisha , Carter Ben , Delibegovic Mirela , Myint Phyo Kyaw
Published: April 2022

Introduction

To date, COVID‐19 has claimed 4.9 million lives. Diabetes has been identified as an independent risk factor of serious outcomes in people with COVID‐19 infection. Whether that holds true across world regions uniformly has not been previously assessed.

Methods

This study offers the first umbrella systematic review and meta‐analysis to analyse the collective and geographically stratified mortality, ICU admission, ventilation requirement, illness severity and discharge rate amongst patients with diabetes. Five databases (EMBASE, MEDLINE, CAB Abstracts, PsychInfo and Web of Science) and 3 additional sources (SSRN's eLibrary, Research Square and MedRxiv) were searched from inception to 30 August 2021. Prospective and retrospective cohort studies, reporting the association between diabetes and one or more COVID‐19 hospitalization outcomes, were included. This meta‐analysis was registered on PROSPERO, CRD42021278579. Abbreviated MeSH terms used for search were as follows: (Diabetes) AND (2019 Novel Coronavirus Disease), adapted per database requirements. Exclusion criteria exclusion criteria were as follows: (1) none of the primary or secondary outcomes of meta‐analysis reported, (2) no confirmed COVID‐19 infection (laboratory or clinical) and (3) no unexposed population (solely patients with diabetes included). Quality of the included studies were assessed using the Newcastle‐Ottawa Scale (NOS) whilst quality of evidence by the GRADE framework. Studies that were clinically homogeneous were pooled. Summative data and heterogeneity were generated by the Cochrane platform RevMan (V. 5.4).

Results

Overall, 158 observational studies were included, with a total of 270,212 of participants, median age 59 [53–65 IQR] of who 56.5% were male. A total of 22 studies originated from EU, 90 from Far East, 16 from Middle East and 30 from America. Data were synthesized with mixed heterogeneity across outcomes. Pooled results highlighted those patients with diabetes were at a higher risk of COVID‐19‐related mortality, OR 1.87 [95%CI 1.61, 2.17]. ICU admissions increased across all studies for patients with diabetes, OR 1.59 [95%CI 1.15, 2.18], a result that was mainly skewed by Far East‐originating studies, OR 1.94 [95%CI 1.51, 2.49]. Ventilation requirements were also increased amongst patients with diabetes worldwide, OR 1.44 [95%CI 1.20, 1.73] as well as their presentation with severe or critical condition, OR 2.88 [95%CI 2.29, 3.63]. HbA1C levels under <70 mmol and metformin use constituted protective factors in view of COVID‐19 mortality, whilst the inverse was true for concurrent insulin use.

Conclusions

Whilst diabetes constitutes a poor prognosticator for various COVID‐19 infection outcomes, variability across world regions is significant and may skew overall trends.
Sputum neutrophil elastase and its relation to pediatric bronchiectasis severity: A cross‐sectional study
Authors: Ali Heba A. , Fouda Eman M. , Salem Mona A. , Abdelwahad Marwa A. , Radwan Heba H.
Published: April 2022

Background and Aims

Sputum neutrophil elastase (NE) is a marker of neutrophilic airway inflammation in bronchiectasis. Yet, not much is known about its role in pediatric bronchiectasis severity. This study aimed to assess the sputum NE value as a biomarker of clinical and radiological severity in pediatric bronchiectasis.

Methods

This was a cross‐sectional study assessing sputum NE in a total of 50 bronchiectasis patients under the age of 18 years—30 patients with cystic fibrosis (CF) and 20 patients with non‐CF bronchiectasis were included. Bronchiectasis severity was assessed using Shwachman–Kulczycki (SK) score, CF‐ABLE score, and CF risk of disease progression score, among CF patients, and bronchiectasis severity index (BSI) and FACED criteria among non‐CF bronchiectasis patients, associations between sputum NE and bronchiectasis severity were assessed in both patient groups.

Results

Sputum NE was directly correlated with C‐reactive protein (r = 0.914, p < 0.001), (r = 0.786, p < 0.001), frequency of exacerbations (r = 0.852, p < 0.001) (r = 0.858, p < 0.001), exacerbations severity (r = 0.735, p = 0.002), (r = 0.907, p < 0.001), and the number of hospital admissions (r = 0.813, p < 0.001), (r = 0.612, p  =0.004) in the last year among CF, and non‐CF bronchiectasis patients, respectively. Additional linear correlations were found between sputum NE, CF risk of disease progression score (p < 0.001), CF‐ABLE score (p < 0.001), and lower forced expiratory volume 1% of predicted (p = 0.017; ρ = −0.8) among CF patients. Moreover, sputum NE was positively correlated with the neutrophil count (p = 0.018), and BSI severity score (p = 0.039; ρ = 0.465) among non‐CF bronchiectasis patients.

Conclusions

Sputum NE may be considered a good biomarker of bronchiectasis severity in both CF and non‐CF bronchiectasis patients, as confirmed by the exacerbations rate, CF risk of disease progression, and BSI scores.
Counseling and prenatal diagnosis in facioscapulohumeral muscular dystrophy: A retrospective study on a 13‐year multidisciplinary approach
Authors: Di Feo Maria Francesca , Bettio Cinzia , Salsi Valentina , Bertucci Emma , Tupler Rossella
Published: April 2022

Background and Aims

This is the first national population‐based report about prenatal diagnosis for families with a history of facioscapulohumeral muscular dystrophy (FSHD), a complex hereditary disease. The incomplete disease penetrance and the phenotypic heterogeneity observed in carriers of D4Z4 alleles of reduced size, the FSHD molecular hallmark, make the estimate of genetic risk problematic.

Methods

We considered all requests of preconception counseling and prenatal diagnosis received between January 2008 and December 2020 by the genetic counseling service associated with the Italian National Registry for FSHD (INRF). A multidisciplinary team managed the clinical and molecular data of each family.

Results

Between 2008 and 2020, 60 couples required preconception counseling (PC) for FSHD. In 52 couples was observed at least one partner carried a D4Z4 reduced allele (DRA). Out of these 52 couples, 47 had a follow‐up visit routine yearly. Out of these 47, 26 (55.3%) couples had children: eight asked for prenatal diagnosis (PND), two had assisted reproduction by heterologous in vitro fertilization (IVF), and 16 did not require further assistance. Regarding PND, 50 prenatal analyses were performed for 36 couples. The test resulted positive in 27 pregnancies, 12 (44.4%) were terminated, and 15 (55.6%) were carried to term.

Conclusion

The different choices made by the couples show the importance of an integrated approach to support genetic counseling for FSHD. These results remark the relevance of the clinical and molecular investigation of the extended family, preferably before conception.
A dynamic ICN and IoT based caching method supporting high‐tech transformation
Authors: Mei Huabin
Published: April 2022

In the Information Center Network (ICN) and Internet of Things (IoT) integrated environment, the existing cache research mainly realizes the cache configuration of high‐tech content in a single dimension such as content popularity or freshness. In view of the above conditions, this paper first analyzes the characteristics of high‐tech transformation, and combines the data characteristics of the Internet of things, divides the data into periodic data and event triggered data. Then, considering these two data characteristics of the Internet of things, an ICN‐IoT cache scheme with different cache decisions is proposed to accelerate the transformation of high‐tech. Simulation results show that the scheme can improve the difference rate of high‐tech content, increase the diversity of cache content, improve the cache hit rate, and then meet the needs of different high‐tech transformation.
Progress on the toxicity of quantum dots to model organism‐zebrafish
Authors: Bai Changcun , Tang Meng
Published: April 2022

In vivo toxicological studies are currently necessary to analyze the probable dangers of quantum dots (QDs) to the environment and human safety, due to the fast expansion of QDs in a range of applications. Because of its high fecundity, cost‐effectiveness, well‐defined developmental phases, and optical transparency, zebrafish has long been considered the “gold standard” for biosafety assessment of chemical substances and pollutants. In this review, the advantages of using zebrafish in QD toxicity assessment were explored. Then, the target organ toxicities such as developmental toxicity, immunotoxicity, cardiovascular toxicity, neurotoxicity, and hepatotoxicity were summarized. The hazardous effects of different QDs, including cadmium‐containing QDs like CdTe, CdSe, and CdSe/ZnS, as well as cadmium‐free QDs like graphene QDs (GQDs), graphene oxide QDs (GOQDs), and others, were emphasized and described in detail, as well as the underlying mechanisms of QDs generating these effects. Furthermore, general physicochemical parameters determining QD‐induced toxicity in zebrafish were introduced, such as chemical composition and surface coating/modification. The limitations and special concerns of using zebrafish in QD toxicity studies were also mentioned. Finally, we predicted that the utilization of high‐throughput screening assays and omics, such as transcriptome sequencing, proteomics, and metabolomics will be popular topic in nanotoxicology.
Clinical outcome of porous hydroxyapatite/collagen graft on bone defects following curettage of bone tumors
Authors: Iwatsu Jun , Watanuki Munenori , Yoshida Shinichirou , Hitachi Shin , Watanabe Mika , Aizawa Toshimi
Published: April 2022

Hydroxyapatite/collagen (HAp/col) has been reported to be a highly useful bone‐like nanocomposite. This study included 33 human patients to investigate the details of the clinical outcomes, which are (1) onset of timing of bone regeneration, (2) replacement by regenerated bone of HAp/col and (3) complications, in human cases grafting HAp/col in large bone defects, following curettage of bone tumors. Porous HAp/col initiated bone regeneration approximately 59 days following the surgery. In 15 cases (45%), complete replacement by newly formed bone was observed 12 months after surgery. On the other hand, incomplete replacement of HAp/col at the final follow‐up was observed in 13 cases (39%). In these cases, HAp/col could not be detected in the transparent area of postoperative plain radiographs owing to quick absorption; moreover, it was difficult to distinguish whether the transparent area in plain radiographs was remaining HAp/col, recurrence, or remaining tumor. In addition, larger HAp/col implantation volume (≧15 cm3) was associated with poorer result of complete replacement (log‐rank, p = .005). Further studies are warranted for the construction of a new artificial bone graft substitute that is more quickly and surely regenerated by newly formed bone in large bone defects.
A novel prognostic model associated with the overall survival in patients with breast cancer based on lipid metabolism‐related long noncoding RNAs
Authors: Shi Guo‐Jian , Zhou Qin , Zhu Qi , Wang Li , Jiang Guo‐Qin
Published: April 2022

Background

Lipid metabolism is closely related to the occurrence and development of breast cancer. Our purpose was to establish a novel model based on lipid metabolism‐related long noncoding RNAs (lncRNAs) and evaluate the potential clinical value in predicting prognosis for patients suffering from breast cancer.

Methods

RNA data and clinical information for breast cancer were obtained from the cancer genome atlas (TCGA) database. Lipid metabolism‐related lncRNAs were identified via the criteria of correlation coefficient |R2| > 0.4 and p < 0.001, and prognostic lncRNAs were identified to establish model through Cox regression analysis. The training set and validation set were established to certify the feasibility, and all samples were separated into high‐risk group or low‐risk group. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were conducted to evaluate the potential biological functions, and the immune infiltration levels were explored through Cibersortx database.

Results

A total of 14 lncRNAs were identified as protective genes (AC022150.4, AC061992.1, AC090948.3, AC092794.1, AC107464.3, AL021707.8, AL451085.2, AL606834.2, FLJ42351, LINC00926, LINC01871, TNFRSF14−AS1, U73166.1 and USP30−AS1) with HRs < 1 while 10 lncRNAs (AC022150.2, AC090948.1, AC243960.1, AL021707.6, ITGB2−AS1, OTUD6B−AS1, SP2−AS1, TOLLIP−AS1, Z68871.1 and ZNF337−AS1) were associated with increased risk with HRs >1. A total of 24 prognostic lncRNAs were selected to construct the model. The patients in low‐risk group were associated with better prognosis in both training set (p < 0.001) and validation set (p < 0.001). The univariate and multivariate Cox regression analyses revealed that risk score was an independent prognostic factors in both training set (p < 0.001) and validation set (p < 0.001). GO and GSEA analyses revealed that these lncRNAs were related to metabolism‐related signal pathway and immune cells signal pathway. Risk score was negatively correlated with B cells (r = −0.097, p = 0.002), NK cells (r = −0.097, p = 0.002), Plasma cells (r = −0.111, p = 3.329e‐04), T‐cells CD4 (r = −0.064, p = 0.039) and T‐cells CD8 (r = −0.322, p = 2.357e‐26) and positively correlated with Dendritic cells (r = 0.077, p = 0.013) and Monocytes (r = 0.228, p = 1.107e‐13).

Conclusion

The prognostic model based on lipid metabolism lncRNAs possessed an important value in survival prediction of breast cancer patients.
Novel immune‐related signature based on immune cells for predicting prognosis and immunotherapy response in clear cell renal cell carcinoma
Authors: Zhou Libin , Fang Hualong , Yin Min , Long Huimin , Weng Guobin
Published: April 2022

Background

Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney and is characterized by poor prognosis. We sought to build an immune‐related prognostic signature and investigate its relationship with immunotherapy response in ccRCC.

Methods

Immune‐related genes were identified by ssGSEA and WGCNA. The prognostic signature was conducted via univariate, least absolute shrinkage and selection operator, and multivariable Cox regression analyses. Kaplan‐Meier analysis, PCA, t‐SNE, and ROC were used to evaluate the risk model.

Results

A total of 119 immune‐related genes associated with prognosis were screened out. Six immune‐related genes (CSF1, CD5L, AIM2, TIMP3, IRF6, and HHLA2) were applied to construct a prognostic signature for KIRC. Kaplan–Meier analysis showed that patients in high‐risk group had a poorer survival outcome than in low‐risk group. The 1‐, 3‐ and 5‐year AUC of the prognostic signature was 0.754, 0.715, and 0.739, respectively. Univariate and multivariate Cox regression models demonstrated that the risk signature was an independent prognostic factor for KIRC survival. GSEA analysis suggested that the high‐risk group was concentrated on immune‐related pathways. The high‐risk group with more regulatory T‐cell infiltration showed a higher expression of immune negative regulation genes. The risk score had positively relationship with TIDE score and negatively with the response of immunotherapy. The IC50 values of axitinib, sunitinib, sorafenib, and temsirolimus were lower in the high‐risk group.

Conclusion

Our study defined a robust signature that may be promising for predicting clinical outcomes and immunotherapy and targeted therapy response in ccRCC patients.
LncRNA PVT1 is increased in renal cell carcinoma and affects viability and migration in vitro
Authors: Bohosova Julia , Kasik Marek , Kubickova Adela , Trachtova Karolina , Stanik Michal , Poprach Alexandr , Slaby Ondrej
Published: April 2022

Background

Renal cell carcinoma is difficult to diagnose and unpredictable in disease course and severity. There are no specific biomarkers for diagnosis and prognosis estimation feasible in clinical practice. Long non‐coding RNAs (lncRNAs) have emerged as potent regulators of gene expression in recent years. Aside from their cellular role, their expression patterns could be used as a biomarker of ongoing pathology.

Methods

In this work, we used next‐generation sequencing for global lncRNA expression profiling in tumor and non‐tumor tissue of RCC patients. The four candidate lncRNAs have been further validated on an independent cohort. PVT1, as the most promising lncRNA, has also been studied using functional in vitro tests.

Results

Next‐generation sequencing showed significant dysregulation of 1163 lncRNAs; among them top 20 dysregulated lncRNAs were AC061975.7, AC124017.1, AP000696.1, AC148477.4, LINC02437, GATA3‐AS, LINC01762, LINC01230, LINC01271, LINC01187, LINC00472, AC007849.1, LINC00982, LINC01543, AL031710.1, and AC019197.1 as down‐regulated lncRNAs; and SLC16A1‐AS1, PVT1, LINC0887, and LUCAT1 as up‐regulated lncRNAs. We observed statistically significant dysregulation of PVT1, LUCAT1, and LINC00982. Moreover, we studied the effect of artificial PVT1 decrease in renal cell line 786–0 and observed an effect on cell viability and migration.

Conclusion

Our results show not only the diagnostic but also the therapeutic potential of PVT1 in renal cell carcinoma.
Start‐up of partial nitrification by intermittent aeration, pH shocks and sulfide addition in a sequential batch reactor
Authors: Hassan Magray Owaes , Gani Khalid M. , Kumari Sheena , Awolusi Oluyemi , Gumede Lethintokozo , Seyam Mohammed , Bux Faizal
Published: April 2022

BACKGROUND

The combination of partial nitrification (PN) and anaerobic ammonium oxidation has been identified as a promising technology for the removal of nitrogenous contaminants from wastewater. The inhibition or wash‐out of nitrite‐oxidizing bacteria (NOB) while keeping the ammonia oxidizing bacteria (AOB) active is key for PN. Multiple strategies, including intermittent aeration, pH shocks and sulfide addition, were investigated in this study for the start‐up of PN and stable suppression of NOB.

RESULTS

Intermittent aeration with a dissolved oxygen (DO) level of <5 mg L−1 effectively suppressed NOB activity and resulted in an average nitrite accumulation (NAR) of 93%, implying that the initial DO level during the aeration phase may influence the establishment of successful PN. Likewise, when the reactor was run at a low pH (5), both AOB and NOB activity was reduced. When the pH was raised to neutral pH (7.5), there was an increase in AOB activity with an average NAR of 84%; however, NOB activity remained suppressed. Likewise, when the reactor was fed with sulfide (≤25 mg L−1) without pH control, the average NAR increased from 63% to 85%.

CONCLUSIONS

This study proposes a successful approach to achieving PN by controlling DO level in the aeration phase during intermittent aeration and pH control. The findings also show that the nitrite oxidation process is more sensitive to sulfide than the ammonium oxidation process. As a result, the findings of this study may contribute to a better understanding of establishing PN in a sequential batch system. © 2022 Society of Chemical Industry (SCI).
Interaction between COMT Val158Met polymorphism and childhood trauma predicts risk for depression in men
Authors: Xavier Janaína , Bastos Clarissa Ribeiro , Camerini Laísa , Amaral Paola Bajadares , Jansen Karen , de Mattos Souza Luciano Dias , da Silva Ricardo Azevedo , Pinheiro Ricardo Tavares , Lara Diogo Rizzato , Ghisleni Gabriele
Published: April 2022

Depression is a disabling illness with complex etiology. While the catechol‐O‐methyltransferase (COMT) gene, in particular the functional Val158Met polymorphism, has been related to depression, the mechanisms underlying this gene‐disease association are not completely understood. Therefore, we explore the association of COMT Val158Met polymorphism with depression as well as its interaction with childhood trauma in 1136 young adults from a population‐based study carried out in the city of Pelotas, Brazil. The diagnosis was performed through the Mini International Neuropsychiatric Interview 5.0 (MINI 5.0), and trauma was assessed with the Childhood Trauma Questionnaire (CTQ). Total DNA was extracted and genotyped by real‐time PCR, and the QTLbase dataset was queried to perform large‐scale quantitative trait locus (QTL) analysis. Our research showed no direct association between the Val158Met polymorphism and the diagnosis of depression (women: χ2 = 0.10, d = 1, p = 0.751; men: χ2 = 0.003, df = 1, p = 0.956). However, the Met‐allele of the Val158Met polymorphism modified the effect of childhood trauma in men (OR = 2.58 [95% CI: 1.05–6.29]; p = 0.038) conferring risk for depression only on those who suffer from trauma. The conditional effect from moderation analysis showed that trauma impacts the risk of depression only in men carrying the Met‐allele (effect: 0.9490, standard error [SE]: 0.2570; p = 0.0002). QTLbase and dataset for Val158Met polymorphism were consistent for markers that influence chromatin accessibility transcription capacity including histone methylation and acetylation. The changes caused in gene regulation by childhood trauma exposure and polymorphism may serve as evidence of the mechanism whereby the interaction increases susceptibility to this disorder in men.
Developing sustainable capacity for urban assemblies: Case study of a World Bank project in Ghana
Authors: Danquah Joseph Kwadwo , Analoui Farhad , Boampong Boakye , Amenshiah Ambrose Kwabena
Published: April 2022

Donor partners have been supporting developing economies in capacity development through donor‐funded projects to enable them to achieve sustainable development. To understand the effectiveness of such projects, this paper adopted a mixed‐methods approach to study a capacity development project funded by the World Bank and implemented in 46 metropolitan and municipal assemblies in Ghana. The study employed the European Centre for Development Policy Management's core capabilities model (5Cs) to examine the World Bank project. The study recommends that, to ensure sustainability, capacity development projects should be embedded in Ghana's development programmes. We also propose an alternative model for the implementation of capacity development projects to achieve sustainable development.
The role of the lateral septum in neuropsychiatric disease
Authors: Patel Hamish
Published: April 2022

The lateral septum (LS) is a structure in the midline of the brain that is interconnected with areas associated with stress and feeding. This review highlights the role of the LS in anxiety, depression, and eating disorders and their comorbidity. There is a prevailing view that the LS is anxiolytic. This review finds that the LS is both anxiolytic and anxiogenic. Furthermore, the LS can promote and inhibit feeding. Given these shared roles, the LS represents a common site for the comorbidity of neuropsychiatric disorders, and therefore a potential pharmacological target. This is crucial since currently available treatments are not always effective. Corticotrophin‐releasing factor 2 antagonists are potential drugs for the treatment of anxiety and anorexia and require further research. Furthermore, other drugs currently in trials for binge eating, such as alpha‐adrenergic agonists, may in fact promote food intake. It is hoped that the advancements in chemo‐ and optogenetic techniques will allow future studies to profile the specific neural connections of the LS and their function. This information could facilitate our understanding of the underlying mechanisms, and therefore pharmacological targets, of these psychiatric conditions.
What does gender has to do with math? Complex questions require complex answers
Authors: Girelli Luisa
Published: April 2022

Whether mathematics is a gendered domain or not is a long‐lasting issue bringing along major social and educational implications. The females' underrepresentation in science, technology, engineering, and mathematics (STEM) has been considered one of the key signs of the math gender gap, although the current view largely attributes the origin of this phenomenon to sociocultural factors. Indeed, recent approaches to math gender differences reached the universal conclusion that nature and nurture exert reciprocal effects on each other, establishing the need for approaching the study of the math gender issue only once its intrinsic complexity has been accepted. Building upon a flourishing literature, this review provides an updated synthesis of the evidence for math gender equality at the start, and for math gender inequality on the go, challenging the role of biological factors. In particular, by combining recent findings from different research areas, the paper discusses the persistence of the “math male myth” and the associated “female are not good at math myth,” drawing attention to the complex interplay of social and cultural forces that support such stereotypes. The suggestion is made that longevity of these myths results from the additive effects of two independent cognitive biases associated with gender stereotypes and with math stereotypes, respectively. Scholars' responsibility in amplifying these myths by pursuing some catching lines of research is also discussed.