bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphorus‐Containing Polymeric Zwitterion: A Pioneering Bioresponsive Probe for 31P‐Magnetic Resonance Imaging
Authors: Kracíková Lucie , Ziółkowska Natalia , Androvič Ladislav , Klimánková Iveta , Červený David , Vít Martin , Pompach Petr , Konefał Rafał , Janoušková Olga , Hrubý Martin , Jirák Daniel , Laga Richard
Published: March 2022

31P‐magnetic resonance (MR) is an important diagnostic technique currently used for tissue metabolites assessing, but it also has great potential for visualizing the internal body structures. However, due to the low physiological level of phosphorus‐containing biomolecules, precise imaging requires the administration of an exogenous probe. Herein, this work describes the synthesis and MR characterization of a pioneering metal‐free 31P‐MR probe based on phosphorus‐containing polymeric zwitterion. The developed probe (pTMPC) is a well‐defined water‐soluble macromolecule characterized by a high content of naturally rare phosphorothioate groups providing a high‐intensity 31P‐MR signal clearly distinguishable from biological background both in vitro and in vitro. In addition, pTMPC can serve as a sensitive 31P‐MR sensor of pathological conditions in vivo because it undergoes oxidation‐induced structural changes in the presence of reactive oxygen species (ROS). Add to this the favorable 1H and 31P T1/T2 relaxation times and biocompatibility, pTMPC represents a conceptually new diagnostic, whose discovery opens up new possibilities in the field of 31P‐MR spectroscopy and imaging.
Measuring image distortions arising from age‐related macular degeneration: An Iterative Amsler Grid (IAG)
Authors: Ayhan Inci , Doyle Edward , Zanker Johannes
Published: March 2022

Metamorphopsia, perceived as distortion of a shape, is experienced in age‐related macular degeneration (AMD): straight lines appear to be curved and wavy to AMD patients and some other retinal pathologies. Conventional clinical assessment largely relies on asking patients to identify irregularities in Amsler Grids ‐ a standardized set of equally spaced vertical and horizontal lines. Perceived distortions or gaps in the grid are a sign of macular pathology. Here, we developed an iterative Amsler Grid (IAG) procedure to obtain a quantifiable map of visual deformations. Horizontal and vertical line segments representing metamorphopsia are displayed on a computer screen. Line segments appearing distorted are adjusted by participants using the computer mouse to change their orientation in several iteratively such that they appear straight. Control participants are able to reliably correct deformations that simulate metamorphopsia while maintaining fixation in the center. In a pilot experiment, we attempted to obtain deformation maps from a small number of AMD patients. Whereas some patients with extensive scotomas found this procedure challenging, others were comfortable using the IAG and generating deformation maps corresponding to their subjective reports. This procedure may potentially be used to quantify local distortions and map them reliably in patients with early AMD.
Tyrosine phosphatase SHP2 exacerbates psoriasis‐like skin inflammation in mice via ERK5‐dependent NETosis
Authors: Ding Yan , Ouyang Zijun , Zhang Chenyang , Zhu Yuyu , Xu Qiang , Sun Haiyan , Qu Jiao , Sun Yang
Published: March 2022

Psoriasis is a chronic inflammatory skin disease, often accompanied by increased infiltration of immune cells, especially neutrophils. However, the detailed mechanism of the neutrophil function in psoriasis progression remains unclear. Here, we found that both Src homology‐2 domain‐containing protein tyrosine phosphatase‐2 (SHP2) and neutrophils were highly correlated to developing psoriasis by single‐cell ribonucleic acid (RNA) sequencing and experiment verification. The deficiency of SHP2 in neutrophils significantly alleviated psoriasis‐like phenotype in an imiquimod‐induced murine model. Interestingly, high levels of neutrophil extracellular traps (NETs) were produced in the inflamed lesions of psoriatic patients. In addition, imiquimod‐induced psoriasis‐like symptoms were remarkably ameliorated in peptidyl arginine deiminase 4 (PAD4) knockout mice, which cannot form NETs. Mechanistically, RNA‐seq analysis revealed that SHP2 promoted the formation of NETs in neutrophils via the ERK5 pathway. Functionally, this mechanism resulted in the infiltration of pro‐inflammatory cytokines such as TNF‐α, IL‐1β, IL‐6, IL‐17A, and CXCL‐15, which enhances the inflammatory response in skin lesions and reinforces the cross‐talk between neutrophils and keratinocytes, ultimately aggravating psoriasis. Our findings uncover a role for SHP2 in NET release and subsequent cell death known as NETosis in the progression of psoriasis and suggest that SHP2 may be a promising therapeutic target for psoriasis.
Antiphospholipid‐Related Chorea: Two Case Reports and Role of Metabolic Imaging
Authors: Lerjefors Lisa , Andretta Silvia , Bonato Giulia , Mainardi Michele , Carecchio Miryam , Antonini Angelo
Published: March 2022

Background

Antiphospholipid syndrome (APS) is a complex acquired autoimmune disease with a wide clinical spectrum. Chorea is a rare neurological manifestation of APS.

Cases

We report two elderly patients with APS‐related chorea in whom functional imaging (18F‐FDG positron emission tomography, FDG‐PET) supported the diagnosis and compare our findings with existing literature.

Literature Review

Among 142 clinical cases of antiphospholipid‐related chorea found in literature, only 10 had undergone brain metabolic imaging. Striatal hypermetabolism was evident in all cases (6) that underwent FDG‐PET cerebral imaging. Cerebral perfusion single photon emission computed tomography (SPECT) was normal in two cases, while the other two presented with basal ganglia hypoperfusion.

Conclusions

Brain FDG‐PET usually shows striatal hypometabolism in neurodegenerative types of chorea as opposed to striatal hypermetabolism observed in most cases of chorea from reversible etiologies, such as APS‐related chorea. When a patient's clinical presentation is not clearly suggestive of either a neurodegenerative or autoimmune chorea, and first‐line investigations are normal, FDG‐PET may help in the differential diagnosis, especially in the presence of striatal hypermetabolism. SPECT data are less numerous and show either normal scans or basal ganglia hypoperfusion.
High‐performance flexible humidity sensors for breath detection and non‐touch switches
Authors: Yao Xingye , Chen Lei , Luo Zewei , Ye Changqing , Liang Fang , Yang Tao , Liu Xingchi , Tian Xiyue , Bi Hengchang , Wang Chaolun , Cai Chunhua , Lyu Liangjian , Wu Xing
Published: March 2022

Flexible humidity sensors have attracted much attention due to the promising applications in medical health monitoring. Up to now, the realization of such devices with ultrafast response/recovery and wide humidity range still remains a challenge. In this work, we report a new type of humidity sensor based on laser‐induced graphene (LIG) and graphene oxide (GO) with excellent performances. Graphene interdigital electrodes with good conductivity were prepared by the laser‐induced method. Then, the GO dispersion was drop‐coated on the interdigital electrode and heated to form a film as a sensing material. We have systematically studied the performances of the humidity sensor under different humidity levels. The experiment results reveal that the humidity sensor possesses high response, fast response/recovery behavior with 2 and 35 seconds, and wide humidity range from 11% RH to 97% RH. This proposed high‐performance humidity sensors could be applied in practical applications such as human breath monitoring under different states including slow breath, normal breath, fast breath, cough and rhinitis. In addition, the humidity sensors could also be used to monitor the approaching of fingertips, which makes the sensors be ideal non‐contact buttons of the elevator for stopping contacting spread of COVID‐19 viruses.
The effect of servant leadership on employees' extra‐role behaviors in NPOs: The role of work engagement
Authors: Aboramadan Mohammed , Hamid Zeeshan , Kundi Yasir Mansoor , El Hamalawi Eissa
Published: March 2022

Building on the social exchange theory and the rule of reciprocity, this study examines the effect of servant leadership on employees' extra‐role behaviors (innovative work behavior, organizational citizenship behavior, and creativity) in the nonprofit organizations (NPOs) context. In this model, we examined work engagement as a mediator. Data were collected in two waves from 309 employees and complemented by their supervisors' evaluations. We analyzed the data using structural equation modeling and the Baron and Kenny method for mediation. The findings reveal that servant leadership exerts a positive influence on employees' extra‐role behaviors. Furthermore, work engagement plays a significant role as a mediator in the relationship between servant leadership and extra‐role behaviors. Finally, discussion, implications, and limitations are presented.
Evaluating opioid analgesic prescribing limits: A narrative review
Authors: Seitz Amy E. , Janiszewski Karen A. , Guy Gery P. , Tapscott Ryan T. , Einstein Emily B. , Meyer Tamra E. , Tierney Jessica , Staffa Judy , Jones Christopher M. , Compton Wilson M.
Published: March 2022

Purpose

In response to the opioid crisis, opioid analgesic guidelines and prescribing limits have proliferated. The purpose of this narrative review is to examine evidence from studies evaluating the patient or public health impact of federal and state opioid analgesic prescribing guidelines and laws, describe gaps and challenges in current research, and highlight opportunities for improving future research.

Methods

We focused on evidence from a literature review covering 2013 through 2019. We identified 30 studies evaluating opioid analgesic thresholds based on federal policies and guidelines, state laws, and Medicaid state plans that attempt to influence the course of patient care at or when the limit is exceeded (e.g., prior authorization).

Results

Most studies evaluated changes in prescribing or dispensing patterns of opioid analgesics, largely finding decreases in prescribing after policy enactment. Fewer studies evaluated patient or public health outcomes beyond changes in prescribing and dispensing patterns; results were infrequently stratified by potentially important sociodemographic and clinical factors. No studies assessed the potential for adverse patient outcomes for which we have emerging evidence of harms.

Conclusions

We describe knowledge gaps and propose opportunities for future research to sufficiently assess the potential impact and unintended consequences of opioid analgesic prescribing laws, regulations, guidelines, and policies.
Antithrombotic Therapy by Regulating the ROS‐Mediated Thrombosis Microenvironment and Specific Nonpharmaceutical Thrombolysis Using Prussian Blue Nanodroplets
Authors: Zhang Wenli , Wang Junrui , Xie Zhuoyan , Zou Hongmi , Chen Qiaoqi , Xu Lian , Hu Liu , Fang Ni , Xu Jie , Zhou Jun , Liu Jia , Ran Haitao , Wang Zhigang , Zhang Yu , Guo Dajing
Published: March 2022

In thrombotic diseases, the effects of reactive oxygen species (ROS)‐mediated oxidative stress as a “perpetrator” in thrombosis must be resolved. Accordingly, an insufficient understanding of thrombus therapy prompted the authors to pursue a more comprehensive and efficient antithrombotic treatment strategy. A Prussian blue (PB)‐based nanodroplet system (PB‐PFP@PC) is designed using PB and perfluorinated pentane (PFP) in the core, and a targeting peptide (CREKA, Cys‐Arg‐Glu‐Lys‐Ala) is attached to poly(lactic‐coglycolic acid) (PLGA) as the delivery carrier shell. Upon near‐infrared (NIR) laser irradiation, PB and PFP jointly achieve an unprecedented dual strategy for drug‐free thrombolysis: photothermal therapy (PTT) combined with optical droplet vaporization (ODV). PB, a nanoenzyme, also regulates the vascular microenvironment via its antioxidant activity to continuously scavenge abnormally elevated ROS and correspondingly reduce inflammatory factors in the thrombus site. This study provides a demonstration of not only the potential of ODV in thrombus therapy but also the mechanism underlying PTT thrombolysis due to thermal ablation‐induced fibrin network structural damage. Moreover, PB catalyzes ROS to generate oxygen (O2), which combines with the ODV effect, enhancing the ultrasound signal. Thus, regulation of the thrombosis microenvironment combined with specific nonpharmaceutical thrombolysis by PB nanodroplets provides a more comprehensive and efficient antithrombotic therapeutic strategy.
Atomically Thin TaSe2 Film as a High‐Performance Substrate for Surface‐Enhanced Raman Scattering
Authors: Ge Yuancai , Wang Fei , Yang Ying , Xu Yi , Ye Ying , Cai Yu , Zhang Qingwen , Cai Shengying , Jiang DanFeng , Liu Xiaohu , Liedberg Bo , Mao Jian , Wang Yi
Published: March 2022

An atomically thin TaSe2 sample, approximately containing two to three layers of TaSe2 nanosheets with a diameter of 2.5 cm is prepared here for the first time and applied on the detection of various Raman‐active molecules. It achieves a limit of detection of 10−10 m for rhodamine 6G molecules. The excellent surface‐enhanced Raman scattering (SERS) performance and underlying mechanism of TaSe2 are revealed using spectrum analysis and density functional theory. The large adsorption energy and the abundance of filled electrons close to the Fermi level are found to play important roles in the chemical enhancement mechanism. Moreover, the TaSe2 film enables highly sensitive detection of bilirubin in serum and urine samples, highlighting the potential of using 2D SERS substrates for applications in clinical diagnosis, for example, in the diagnosis of jaundice caused by excess bilirubin in newborn children.
Post‐fire behavior of steel slag fine aggregate concrete
Authors: Zhuang Xin , Liang Yi , Ho Johnny Ching Ming , Wang Yu‐Hang , Lai Mianheng , Li Xuanyang , Xu Zhenhai , Xu Yuning
Published: March 2022

Using steel slag fine aggregate (SSFA) to replace river sand (RS) in making concrete offers a sustainable solution for mitigating the environmental issues owing to the large‐scale mining of RS and disposal of a large amount of steel slag. The mechanical behavior and chemical property of concrete made with SSFA at ambient temperature were investigated extensively. However, relatively few studies have been conducted to investigate the behavior of concrete with SSFA after exposure to elevated temperatures. To fill up this research gap, this paper studied the post‐fire behavior of five concrete mixes with SSFA replacing RS. The effect of SSFA replacement ratio by volume (0%, 25%, 50%, 75%, and 100%) on the heating temperature—time curve, color and appearance changes, weight loss, failure mode, and residual compressive strength of concrete under curing period of 28‐ and 91‐day, after exposure to 25 (ambient temperature), 400, 600, 800, and 1000°C was investigated. Besides, chemical composition at ambient and after exposure to elevated temperatures was analyzed with the aid of X‐ray diffraction. Test results showed that with SSFA partially or totally replacing RS, the heat insulation capability of concrete could be enhanced, especially at the replacement ratio of 75%. Moreover, concrete with RS replaced with SSFA presented larger or comparable residual strength after exposure to elevated temperatures from 600–800°C. Lastly, the design model by EC2 was adopted to predict the residual strength of concrete with and without SSFA. Comparing the design and measured residual strengths, it was concluded that EC2 was conservative.
Met–HER3 crosstalk supports proliferation via MPZL3 in MET-amplified cancer cells
Authors: Stern Yaakov E. , Al-Ghabkari Abdulhameed , Monast Anie , Fiset Benoit , Aboualizadeh Farzaneh , Yao Zhong , Stagljar Igor , Walsh Logan A. , Duhamel Stephanie , Park Morag
Published: March 2022

Receptor tyrosine kinases (RTKs) are recognized as targets of precision medicine in human cancer upon their gene amplification or constitutive activation, resulting in increased downstream signal complexity including heterotypic crosstalk with other RTKs. The Met RTK exhibits such reciprocal crosstalk with several members of the human EGFR (HER) family of RTKs when amplified in cancer cells. We show that Met signaling converges on HER3–tyrosine phosphorylation across a panel of seven MET-amplified cancer cell lines and that HER3 is required for cancer cell expansion and oncogenic capacity in vitro and in vivo. Gene expression analysis of HER3-depleted cells identified MPZL3, encoding a single-pass transmembrane protein, as HER3-dependent effector in multiple MET-amplified cancer cell lines. MPZL3 interacts with HER3 and MPZL3 loss phenocopies HER3 loss in MET-amplified cells, while MPZL3 overexpression can partially rescue proliferation upon HER3 depletion. Together, these data support an oncogenic role for a HER3–MPZL3 axis in MET-amplified cancers.
Total elbow arthroplasty in elderly trauma patients: adding a new perspective for functional evaluation
Authors: Mühlenfeld Nils , Marzi Ingo , Frank Johannes
Published: March 2022

Purpose

Total elbow arthroplasty (TEA) has evolved over the last years, with satisfactory early results, mainly not only in degenerative arthritis, but also increasingly after trauma. Outcome studies in recently published papers are mainly based on the range of motion (ROM), complication rate as well as patient-reported outcome scales and questionnaires. The purpose of this study was to add a new perspective with the “Purdue Pegboard” skill tests in a homogenous set of elderly trauma patients to contribute to a more precise objective outcome measurement in this specific population.

Methods

A retrospective review was performed on a consecutive cohort of all patients with age above 60 years that received TEA after trauma. Data from follow-up examinations over a standardized time-schedule within 2 years after TEA were included. Mayo Elbow Performance Score (MEPS), “Disability of Arm, Shoulder and Hand” (DASH) Questionnaire, ROM as well as test-scores using the Pegboard test were evaluated.

Results

Mean age was 76.0 years ± 10.3. Indications for TEA were posttraumatic arthrosis in 68.8% (n = 11) and extensive fractures that could not be reconstructed surgically in 31.3% (n = 5). The mean score of MEPS was 82.81 ± 16.63 and 29.18 ± 12.01 in the DASH. ROM presented with a mean of 109.7° ± 15.4. Patients demonstrated good, but marginally reduced test scores in the Pegboard skill tests in comparison with the healthy reference population. No relevant differences between the arm with and the arm without TEA (0.3 ± 3.6; p = 0.715) were noted after 2 years.

Conclusion

In the elderly trauma patient with complex fractures of the elbow, TEA is a good alternative to joint reconstruction using various osteosynthesis techniques. TEA is able to avoid revision surgery after open reduction and internal fixation of complex fractures. In cases of failed reconstruction, it is also a viable secondary procedure in posttraumatic arthrosis. Good outcomes in functionality and dexterity can be achieved. Skill tests like the Purdue Pegboard could add a valuable perspective in assessing functional outcomes after TEA.
Reversibility of brain glucose kinetics in type 2 diabetes mellitus
Authors: Sanchez-Rangel Elizabeth , Gunawan Felona , Jiang Lihong , Savoye Mary , Dai Feng , Coppoli Anastasia , Rothman Douglas L. , Mason Graeme F. , Hwang Janice Jin
Published: March 2022

Aims/hypothesis

We have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by 1H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA1c normalise intracerebral glucose levels.

Methods

Eight individuals (two men, six women) with poorly controlled type 2 diabetes and mean ± SD age 44.8 ± 8.3 years, BMI 31.4 ± 6.1 kg/m2 and HbA1c 84.1 ± 16.2 mmol/mol (9.8 ± 1.4%) underwent 1H MRS scanning at 4 Tesla during a hyperglycaemic clamp (~12.21 mmol/l) to measure changes in cerebral glucose at baseline and after a 12 week intervention that improved glycaemic control through the use of continuous glucose monitoring, diabetes regimen intensification and frequent visits to an endocrinologist and nutritionist.

Results

Following the intervention, mean ± SD HbA1c decreased by 24.3 ± 15.3 mmol/mol (2.1 ± 1.5%) (p=0.006), with minimal weight changes (p=0.242). Using a linear mixed-effects regression model to compare glucose time courses during the clamp pre and post intervention, the pre-intervention brain glucose level during the hyperglycaemic clamp was significantly lower than the post-intervention brain glucose (p<0.001) despite plasma glucose levels during the hyperglycaemic clamp being similar (p=0.266). Furthermore, the increases in brain glucose were correlated with the magnitude of improvement in HbA1c (r = 0.71, p=0.048).

Conclusion/interpretation

These findings highlight the potential reversibility of cerebral glucose transport capacity and metabolism that can occur in individuals with type 2 diabetes following improvement of glycaemic control.

Trial registrationClinicalTrials.gov NCT03469492.

Graphical abstract
Young-onset diabetes in Asian Indians is associated with lower measured and genetically determined beta cell function
Authors: Siddiqui Moneeza K. , Anjana Ranjit Mohan , Dawed Adem Y. , Martoeau Cyrielle , Srinivasan Sundararajan , Saravanan Jebarani , Madanagopal Sathish K. , Taylor Alasdair , Bell Samira , Veluchamy Abirami , Pradeepa Rajendra , Sattar Naveed , Venkatesan Radha , Palmer Colin N. A. , Pearson Ewan R. , Mohan Viswanathan
Published: March 2022

Aims/hypothesis

South Asians in general, and Asian Indians in particular, have higher risk of type 2 diabetes compared with white Europeans, and a younger age of onset. The reasons for the younger age of onset in relation to obesity, beta cell function and insulin sensitivity are under-explored.

Methods

Two cohorts of Asian Indians, the ICMR-INDIAB cohort (Indian Council of Medical Research-India Diabetes Study) and the DMDSC cohort (Dr Mohan’s Diabetes Specialties Centre), and one of white Europeans, the ESDC (East Scotland Diabetes Cohort), were used. Using a cross-sectional design, we examined the comparative prevalence of healthy, overweight and obese participants with young-onset diabetes, classified according to their BMI. We explored the role of clinically measured beta cell function in diabetes onset in Asian Indians. Finally, the comparative distribution of a partitioned polygenic score (pPS) for risk of diabetes due to poor beta cell function was examined. Replication of the genetic findings was sought using data from the UK Biobank.

Results

The prevalence of young-onset diabetes with normal BMI was 9.3% amongst white Europeans and 24–39% amongst Asian Indians. In Asian Indians with young-onset diabetes, after adjustment for family history of type 2 diabetes, sex, insulin sensitivity and HDL-cholesterol, stimulated C-peptide was 492 pmol/ml (IQR 353–616, p<0.0001) lower in lean compared with obese individuals. Asian Indians in our study, and South Asians from the UK Biobank, had a higher number of risk alleles than white Europeans. After weighting the pPS for beta cell function, Asian Indians have lower genetically determined beta cell function than white Europeans (p<0.0001). The pPS was associated with age of diagnosis in Asian Indians but not in white Europeans. The pPS explained 2% of the variation in clinically measured beta cell function, and 1.2%, 0.97%, and 0.36% of variance in age of diabetes amongst Asian Indians with normal BMI, or classified as overweight and obese BMI, respectively.

Conclusions/interpretation

The prevalence of lean BMI in young-onset diabetes is over two times higher in Asian Indians compared with white Europeans. This phenotype of lean, young-onset diabetes appears driven in part by lower beta cell function. We demonstrate that Asian Indians with diabetes also have lower genetically determined beta cell function.

Graphical abstract
Impact of wheat aleurone on biomarkers of cardiovascular disease, gut microbiota and metabolites in adults with high body mass index: a double-blind, placebo-controlled, randomized clinical trial
Authors: Fava Francesca , Ulaszewska Maria M. , Scholz Matthias , Stanstrup Jan , Nissen Lorenzo , Mattivi Fulvio , Vermeiren Joan , Bosscher Douwina , Pedrolli Carlo , Tuohy Kieran M.
Published: March 2022

Purpose

Aleurone is a cereal bran fraction containing a variety of beneficial nutrients including polyphenols, fibers, minerals and vitamins. Animal and human studies support the beneficial role of aleurone consumption in reducing cardiovascular disease (CVD) risk. Gut microbiota fiber fermentation, polyphenol metabolism and betaine/choline metabolism may in part contribute to the physiological effects of aleurone. As primary objective, this study evaluated whether wheat aleurone supplemented foods could modify plasma homocysteine. Secondary objectives included changes in CVD biomarkers, fecal microbiota composition and plasma/urine metabolite profiles.

Methods

A parallel double-blind, placebo-controlled and randomized trial was carried out in two groups of obese/overweight subjects, matched for age, BMI and gender, consuming foods supplemented with either aleurone (27 g/day) (AL, n = 34) or cellulose (placebo treatment, PL, n = 33) for 4 weeks.

Results

No significant changes in plasma homocysteine or other clinical markers were observed with either treatment. Dietary fiber intake increased after AL and PL, animal protein intake increased after PL treatment. We observed a significant increase in fecal Bifidobacterium spp with AL and Lactobacillus spp with both AL and PL, but overall fecal microbiota community structure changed little according to 16S rRNA metataxonomics. Metabolomics implicated microbial metabolism of aleurone polyphenols and revealed distinctive biomarkers of AL treatment, including alkylresorcinol, cinnamic, benzoic and ferulic acids, folic acid, fatty acids, benzoxazinoid and roasted aroma related metabolites. Correlation analysis highlighted bacterial genera potentially linked to urinary compounds derived from aleurone metabolism and clinical parameters.

Conclusions

Aleurone has potential to modulate the gut microbial metabolic output and increase fecal bifidobacterial abundance. However, in this study, aleurone did not impact on plasma homocysteine or other CVD biomarkers.

Trial Registration

The study was registered at ClinicalTrials.gov (NCT02067026) on the 17th February 2014.
Physiological relevance of proton-activated GPCRs
Authors: Imenez Silva Pedro H. , Wagner Carsten A.
Published: March 2022

The detection of H+ concentration variations in the extracellular milieu is accomplished by a series of specialized and non-specialized pH-sensing mechanisms. The proton-activated G protein–coupled receptors (GPCRs) GPR4 (Gpr4), TDAG8 (Gpr65), and OGR1 (Gpr68) form a subfamily of proteins capable of triggering intracellular signaling in response to alterations in extracellular pH around physiological values, i.e., in the range between pH 7.5 and 6.5. Expression of these receptors is widespread for GPR4 and OGR1 with particularly high levels in endothelial cells and vascular smooth muscle cells, respectively, while expression of TDAG8 appears to be more restricted to the immune compartment. These receptors have been linked to several well-studied pH-dependent physiological activities including central control of respiration, renal adaption to changes in acid–base status, secretion of insulin and peripheral responsiveness to insulin, mechanosensation, and cellular chemotaxis. Their role in pathological processes such as the genesis and progression of several inflammatory diseases (asthma, inflammatory bowel disease), and tumor cell metabolism and invasiveness, is increasingly receiving more attention and makes these receptors novel and interesting targets for therapy. In this review, we cover the role of these receptors in physiological processes and will briefly discuss some implications for disease processes.
Healthcare utilization and costs following non-fatal powdered and non-powdered firearm injuries for children and youth
Authors: de Oliveira Claire , Macpherson Alison , Hepburn Charlotte Moore , Huang Anjie , Strauss Rachel , Liu Ning , Fiksenbaum Lisa , Pageau Paul , Gomez David , Saunders Natasha Ruth
Published: March 2022

Little is known about the healthcare and economic burdens of non-fatal firearm injuries for children/youth beyond the initial admission. This study sought to estimate healthcare utilization and total direct healthcare costs of non-fatal powdered and non-powdered (air gun) firearm injuries 1-year post-injury. Using administrative data from 2003 to 2018 on all children/youth 0–24 years old in Ontario, Canada, a matched 1:2 cohort study was conducted to compare children/youth who experienced powdered and non-powdered firearm injuries with those who did not. Mean and median number of healthcare encounters and costs, and respective 95% confidence intervals (CIs) and interquartile ranges (IQRs), were estimated for both weapon type groups and controls and by intent. Children/youth who experienced a powdered and non-powdered firearm injury had a higher number of healthcare encounters and costs per year than those who did not. Mean 1-year costs for those with powdered and non-powdered firearm injuries were $8825 ($8007–$9643) and $2349 ($2118–$2578), respectively, versus $812 ($567–$1058) and $753 ($594–$911), respectively, for those without. Mean 1-year costs were highest for handgun injuries ($12,875 [95% CI $9941–$15,808]), and for intentional assault-related ($13,498 [$11,843–$15,153]; $3287 [$2213–$4362]), and intentional self-injuries ($14,773 [$6893–$22,652]; $6005 [$2193–$9817]) for both powdered and non-powdered firearm injuries, respectively.

   Conclusion: Firearm injuries have substantial healthcare and economic burdens beyond the initial injury-related admission; this should be accounted for when examining the overall impact of firearm injuries.

What is Known:• Child/youth firearm injuries have significant health and economic burdens.• However, existing work has mainly examined healthcare utilization and costs of initial admissions and/or have been limited to single-center studies and no studies have provide cost estimates by weapon type and intent.

What is New:• Children/youth who suffered powdered firearm injuries had higher mean healthcare utilization and costs than those with non-powdered firearm injuries as well as comparable healthy children/youth.• Mean 1-year costs were highest for handgun injuries ($12,875), and for intentional assault-related ($13,498; $3287), and intentional self-injuries ($14,773; $6005) for powdered and non-powdered firearm injuries, respectively.
Response prediction in patients with gastric and esophagogastric adenocarcinoma under neoadjuvant chemotherapy using targeted gene expression analysis and next-generation sequencing in pre-therapeutic biopsies
Authors: Kleo Karsten , Jovanovic Vladimir M. , Arndold Alexander , Lehmann Annika , Lammert Hedwig , Berg Erika , Harloff Hannah , Treese Christoph , Hummel Michael , Daum Severin
Published: March 2022

Objectives

Perioperative chemo-(radio-) therapy is the accepted standard in European patients with locally advanced adenocarcinoma of the esophagogastric junction or stomach (AEG/AS). However, 30–85% of patients do not respond to this treatment. The aim of our study was the identification of predictive biomarkers in pre-therapeutic endoscopic tumor biopsies from patients with histopathologic response (Becker-1) versus non-response (Becker-2/3) to preoperative chemotherapy.

Methods

Formalin-fixed paraffin-embedded biopsies from 36 Caucasian patients (Becker-1 n = 11, Becker-2 n = 7, Becker-3 n = 18) with AEG/AS, taken prior to neoadjuvant chemotherapy were selected. For RNA expression analysis, we employed the NanoString nCounter System. To identify genomic alterations like single nucleotide variants (SNV), copy number variation (CNV) and fusion events, we used Illumina TST170 gene panel. For HER2 and FGFR2 protein expression, immunostaining was performed. Furthermore, we analyzed the microsatellite instability (MSI) and Epstein–Barr virus (EBV) infection status by EBER in situ hybridization.

Results

Heat map and principal component analyses showed no clustering by means of gene expression according to regression grade. Concerning two recently proposed predictive markers, our data showed equal distribution for MSI (Becker-1: 2; Becker-2: 1; Becker-3: 3; out of 29 tested) and EBV infection was rare (1/32). We could not reveal discriminating target genes concerning SNV, but found a higher mutational burden in non-responders versus responders and fusion (in 6/14) and CNV events (in 5/14) exclusively in Becker-3.

Conclusions

Although we could not identify discriminating target genes, our data suggest that molecular alterations are in general more prevalent in patients with AEG/AS belonging to the non-responding Becker group 3.
High clutch failure rate due to unpredictable rainfall for an ephemeral pool-breeding frog
Authors: Gould John , Clulow John , Clulow Simon
Published: March 2022

Animals that reproduce in temporary aquatic systems expose their offspring to a heightened risk of desiccation, as they must race to complete development and escape before water levels recede. Adults must therefore synchronise reproduction with the changing availability of water, yet the conditions they experience to trigger such an event may not relate to those offspring face throughout development, potentially leading to clutch failure. The sandpaper frog (Lechriodus fletcheri) breeds in ephemeral pools that dry within days to weeks after rainfall has ceased. We examined whether spawning frequency and offspring survival differed across two consecutive breeding seasons based on (1) rainfall at the moment of oviposition and throughout offspring development, and (2) pool volume, given their combined effect on hydroperiod. Reproduction was triggered by rainfall, with more spawn laid during periods of greater rainfall and in larger pools. While pool size was a predictor of offspring survival, rainfall during oviposition was not. Rather, follow-up rain events were required to prevent pools drying prior to metamorphosis, with rainfall evenness during development the strongest predictor of reproductive success. High clutch failure rates recorded in both seasons suggest that adults do not have the capability to predict rainfall frequency post-oviposition. We thus conclude that unpredictable rainfall leading to premature desiccation of spawning sites is the primary source of pre-metamorphic mortality for this species. Understanding the influence of rainfall predictability on offspring survival could be critical in predicting the effects of altered hydroperiod regimes due to climate change for species that exploit temporary waters.
Application of ABR in pathogenic neurovascular compression of the 8th cranial nerve in vestibular paroxysmia
Authors: Sun Huiying , Tian Xu , Zhao Yang , Jiang Hong , Gao Zhiqiang , Wu Haiyan
Published: March 2022

Purpose

To investigate the clinical value of electrophysiological tests in indicating pathogenic vascular contact of the 8th nerve in definite vestibular paroxysmia (VP) cases to provide a reference for decompression surgery.

Methods

We retrospectively analyzed patients who had vertigo, unilateral tinnitus, or hearing loss and exhibited vascular contact of the 8th cranial nerve by MRI. Participants were classified into the VP or non-VP group according to the criteria of the Bárány Society in 2016. The demographic characteristics and audiological and electrophysiological test results of the two groups were compared. Receiver operating characteristic (ROC) curves were calculated for ABR to determine the best parameters and cutoff values to predict the existence of pathological neurovascular contact in VP.

Results

Thirteen patients in the VP group and 66 patients in the non-VP group were included. VP patients had longer interpeak latency (IPL) I–III and wave III latency compared to non-VP patients (p < 0.001; p < 0.001). According to the ROC analyses, IPL I–III and wave III latency were the best indicators for the diagnosis of VP. The optimal cutoff for IPL I–III was 2.3 ms (sensitivity 84.6%, specificity 95.5%), and that for wave III latency was 4.0 ms (sensitivity 92.3%, specificity 77.3%). There were no differences in the PTA, caloric test, o-VEMP, or c-VEMP results between the two groups.

Conclusion

Prolonged IPL I–III and the wave III latency of ABR strongly suggested that vascular contact of the 8th cranial nerve was pathological, which may provide some references for microvascular decompression surgery of VP.
Evolution of LNAPL contamination plume in fractured aquifers
Authors: Mineo Simone , Dell’Aera Filippo Maria Luigi , Rizzotto Maria
Published: March 2022

The LNAPL contamination affecting an industrial area of southeastern Sicily (Italy) is reported herein as a case study to analyze some peculiarities on its spatial evolution. The free-phase product of light hydrocarbons, leaked from a tank, deserved investigations due to its anomalous migration trend, which was not consistent with the static groundwater flow direction of the area. The collection of geological and hydrogeological data and their organization into a GIS database allowed reconstructing the evolutionary stage of the plume within the 2014–2020 time interval, providing some explanation to the scientific problem. The supernatant thickness was compared with the groundwater oscillation, leading to consideration on the aquifer typology. The causes of the peculiar migration trend were found in three main factors, among which the geological and geostructural ones gain a key relevance. Achieved results show that the rock mass fracturing and the presence of underground structures, probably of tectonic origin, are responsible in driving the contamination plume through a preferential path under the dynamic condition induced by anthropic activities. This supports the need of underground geological and geostructural knowledge when dealing with similar issues and when designing specific remediation measures; the case study presented herein demonstrates that the correct location of remedial measures is crucial for reclamation purposes. Furthermore, data were statistically analyzed looking for a relation between real and apparent supernatant thickness. Prediction equations, for a quick estimation of the contamination entity in such type of aquifers, are presented providing hints for future studies on other settings worldwide.
Scientific laws of research funding to support citations and diffusion of knowledge in life science
Authors: Mosleh Melika , Roshani Saeed , Coccia Mario
Published: March 2022

One of the main problems in scientometrics is to explore the factors that affect the growth of citations in publications to identify best practices of research policy to increase the diffusion of scientific research and knowledge in science and society. The principal purpose of this study is to analyze how research funding affects the citation-based performance of scientific output in vital research fields of life science, which is a critical province (area of knowledge) in science to improve the wellbeing of people. This study uses data from the Scopus database in 2015 (to assess the impact on citations in 2021, after more than 5 years) concerning different disciplines of life science, given by “agricultural and biological sciences”, “biochemistry, genetics, and molecular biology”, “Immunology and microbiology”, “neuroscience” and “pharmacology, toxicology and pharmaceutics”. Results demonstrate that although journals publish un-funded articles more than funded publications in all disciplines of life science, the fraction of total citations in funded papers is higher than the share in the total number of publications. In short, funded documents receive more citations than un-funded papers in all research fields of life science under study. Findings also support that citations of total (funded + un-funded), funded, and un-funded published papers have a power-law distribution in all five research fields of life science. Original results here reveal a general property in scientific development: funded research has a higher scaling potential than un-funded publications. Critical implications of research policy, systematized in a decision-making matrix, suggest that R&D investments in “Neuroscience” can generate a positive impact of scientific results in science and society-in terms of citations-higher than other research fields in medicine. Overall, then, results here can explain some characteristics driving scientific change and help policymakers and scholars to allocate resources towards research fields that facilitate the development and diffusion of scientific research and knowledge in life science for positive societal impact.
CT evaluation of lung infiltrates in the two months preceding the Coronavirus disease 19 pandemic in Canton Ticino (Switzerland): were there suspicious cases before the official first case?
Authors: Rizzo Stefania , Catanese Carola , Puligheddu Carla , Epistolio Samantha , Ramelli Giulia , Frattini Milo , Pereira Mestre Ricardo , Nadarajah Navarajah , Rezzonico Ermidio , Magoga Francesco , Milan Lisa , Del Grande Filippo , Giovanella Luca , Ceriani Luca
Published: March 2022

Purpose

The main objective of this study was to assess the presence of pulmonary infiltrates with computed tomography (CT) appearance compatible with infection by coronavirus disease 2019 (COVID-19), in Canton Ticino in the 2 months preceding the first official case. Secondary aims were to compare the classification of infiltrates in the same time frame in 2020 and 2019; to compare the number of chest CT scans in the same period; to search for pathological confirmation of the virus.

Materials and methods

Chest CT scans performed between January 1 and February 24 in 2019 and 2020 were collected and classified by COVID-19 Reporting and Data System (CO-RADS). Pathological presence of the virus was searched for when appropriate material was available.

Results

The final cohort included 881 patients. Among the CO-RADS 3 and 4 categories, 30 patients had pneumonitis of unknown etiology. Pathological specimens were available in six patients but they were negative for COVID-19.

Conclusion

Before the first official case of COVID-19 infection, in Canton Ticino there were about 30 cases of pneumonitis of uncertain origin, with CT appearance compatible with infection by COVID-19, but with no confirmation of the disease. The number of chest CT scans in the first two months of 2020 was > 12% compared to 2019.
Algorithm-based design of mechanical joining processes
Authors: Jäckel Mathias , Falk Tobias , Drossel Welf-Guntram
Published: March 2022

In this paper, the development of algorithm-based process models for the mechanical joining process self-pierce riveting with semi-tubular rivet (SPR-ST) is described. Therefore, an extensive experimental and numerical database regarding the SPR-ST process and strength of steel and aluminum joints with tensile strengths of the sheets between 200 and 1000 MPa was generated for the building of the models. This process data could then be used for the training and evaluation of different prediction algorithms. Furthermore, the simulation data is applied to predict the entire contour (mesh) of non-simulated joints. This includes the visualization of output values such as strains, stresses and damage for each element and node of the mesh. That approach enables to obtain more information about the joint than just discrete values such as interlock or strength.
Room for Improvement: How does the Media Portray Individuals Who Engage in Material Depicting Child Sexual Abuse?
Authors: Christensen Larissa S. , Pollard Katarina
Published: March 2022

The media has a powerful ability to shape public perceptions. Given the current disjuncture between social attitudes and the law in relation to child sexual abuse material (CSAM) it is important to explore the representation of CSAM offenders in the media. The aim of this exploratory study was to identify how CSAM offenders are depicted in the print media. Newspaper articles published from 1 August 2019 to 31 August 2020 on CSAM offenders in Western countries were searched. A qualitative content analysis was employed, revealing three themes across the 56 articles: (1) the headings of the articles downplayed the abusive offending; (2) offender’s motivations indicate heterogeneity in offending; and (3) sentencing remarks communicated denunciation and the harms of offending. While the first theme identified that there is still space for improvement in the reporting of these crimes, the second theme indicates the various motivations portrayed should assist the public in identifying that these offenders are heterogenous in their motivations, thus potentially countering some previously held stereotypes. Finally, the denunciation and the harms taken from the messages delivered by the judiciary in the sentencing remarks could offer a positive educational tool for some members of the public. These findings should be valuable for media, law enforcement, and psychology disciplines.
Two experimental studies on the differential effects of low and high treatability information on the inclination to engage in cancer prevention
Authors: Wu Yingqiu , Dijkstra Arie , Dalley Simon E.
Published: March 2022

Two 3(control versus LTI versus HTI) × 2(self-affirmation versus no self-affirmation)-experiments were conducted. The first study presented a news message on the treatability of bowel cancer (N = 717); the second study was about skin cancer (N = 342). The dependent variables were the intention to engage in preventive behaviors and message acceptance. The results showed that when participants were exposed to LTI, only when response efficacy was low, a self-affirmation procedure increased their intention to prevent cancer (experiment 1), and increased message acceptance (experiment 2). When participants were exposed to HTI, the self-affirmation procedure did not increase the intention, and even reduced message acceptance. The findings suggest that defensive processes were active in reaction to LTI, but not in reaction to HTI. Although publishing LTI and HTI information in the media serves legitimate goals, it may have positive but also negative unintended effects on preventive behaviors in the population.