bluuebunny/crossref_metadata_2025 huggingface dataset:
Testicular cancer in mice: interplay between stem cells and endocrine insults
Authors: Kaushik Ankita , Bhartiya Deepa
Published: June 2022

Background

Incidence of type II germ cell tumors (T2GCT) has increased in young men possibly due to fetal/perinatal exposure to estrogenic compounds. Three-fold increased incidence of T2GCT was reported in men exposed in utero to diethylstilbestrol (DES). T2GCT is a development-related disease arising due to blocked differentiation of gonocytes into spermatogonia in fetal testes which survive as germ cell neoplasia in situ (GCNIS) and initiate T2GCT. In our earlier study, T2GCT-like features were observed in 9 out of 10 adult, 100-day-old mice testes upon neonatal exposure to DES (2 μg/pup/day on days 1–5). Neonatal DES exposure affected testicular very small embryonic-like stem cells (VSELs) and spermatogonial stem cells and resulted in infertility, reduced sperm counts and tumor-like changes leading to our postulate that testicular dysgenesis syndrome possibly has a stem cell basis. The present study was undertaken to further characterize testicular tumor in mice testes.

Methods

DES-exposed mice pups (n = 70) were studied on D100 and after 12 months to understand how T2GCT progresses. Besides histological studies, a carefully selected panel of markers were studied by immuno-fluorescence and qRT-PCR.

Results

DES resulted in either atrophied or highly vascularized, big-sized testes and extra-testicular growth was also observed. GCNIS-like cells with big, vacuolated cytoplasm and increased expression of OCT-4, SSEA-1, SCA-1 and CD166 (cancer stem cells marker) along with reduced c-KIT, MVH and PTEN were evident. Global hypomethylation was found associated with altered expression of Dnmts, Igf2-H19 and Dlk-Meg3 imprinted genes along with reduced expression of Ezh2, cell cycle regulator p57KIP2 and Meg3; however, Pten remained unaltered. Increased expression of PCNA and Ki67 was observed in concert with complete lack of SOX-9 suggesting Sertoli cells independent proliferation.

Conclusions

Mouse model for T2GCT is described which will have immense potential to understand cancer initiation, cancer stem cells and also to develop effective therapies in future. T2GCT initiates from tissue-resident, pluripotent VSELs due to their altered epigenome. Neonatal exposure to DES blocks differentiation (spermatogenesis) and VSELs get transformed into CD166 positive cancer stem cells that undergo excessive self-renewal and initiate cancer in adult life challenging existing concept of fetal origin of T2GCT.
Tauroursodeoxycholic acid (TUDCA) improves intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets
Authors: Song Min , Zhang Fenglin , Fu Yiming , Yi Xin , Feng Shengchun , Liu Zhichang , Deng Dun , Yang Qiang , Yu Miao , Zhu Canjun , Zhu Xiaotong , Wang Lina , Gao Ping , Shu Gang , Ma Xianyong , Jiang Qingyan , Wang Songbo
Published: June 2022

Background

Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, is the main medicinal component of bear bile and is commonly used to treat a variety of hepatobiliary diseases. Meanwhile, TUDCA has been shown to modulate the intestinal barrier function and alleviate DSS-induced colitis in mice. However, the effect of TUDCA on the intestinal barrier of weaned piglets remains largely unclear.

Methods

The weaned piglets and porcine IPEC-J2 intestinal epithelial cells were used to investigate the effects of TUDCA on intestinal barrier function in weaned piglets and explore the possible underlying mechanisms. In vivo, 72 healthy weaned piglets were randomly allocated into 2 groups according to their gender and body weight, and piglets were fed the basal diet with 0 (control, CON) and 200 mg/kg TUDCA for 30 d, respectively. Three female and three male piglets reflecting the average bodyweight were slaughtered in each group and samples were collected. In vitro, IPEC-J2 cells were subjected to 100 μmol/L TUDCA to explore the possible underlying mechanisms.

Results

Our results demonstrated that dietary TUDCA supplementation significantly reduced the diarrhea incidence of weaned piglets, possibly attributing to the TUDCA-enhanced intestinal barrier function and immunity. In addition, TUDCA supplementation altered serum metabolites and the relative abundance of certain gut bacteria, which might contribute to the improved intestinal barrier function. Furthermore, the in-vitro results showed that TUDCA improved the E. coli-induced epithelial barrier impairment of IPEC-J2 cells and increased Takeda G-coupled protein receptor 5 (TGR5) protein expression. However, knockdown of TGR5 and inhibition of myosin light chain kinase (MLCK) pathway abolished the TUDCA-improved epithelial barrier impairment in E. coli-treated IPEC-J2 cells, indicating the involvement of TGR5-MLCK in this process.

Conclusions

These findings showed that TUDCA improved intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets, suggesting the potential application of TUDCA in improving gut health in piglet production.
Synergistic interaction of thymol with Piper ribesioides (Piperales: Piperaceae) extracts and isolated active compounds for enhanced insecticidal activity against Spodoptera exigua (Lepidoptera: Noctuidae)
Authors: Kumrungsee Nutchaya , Dunkhunthod Benjawan , Manoruang Wasan , Koul Opender , Pluempanupat Wanchai , Kainoh Yooichi , Yooboon Thitaree , Piyasaengthong Narisara , Bullangpoti Vasakorn , Nobsathian Saksit
Published: June 2022

Background

Plant secondary metabolites or mixtures in extracts or essential oils are well known to enhance the activity in binary mixtures. The present study is the first to report that thymol synergistically or additively enhances the activity of P. ribesioides extracts and isolated compounds against S. exigua larvae at sublethal doses.

Results

Thymol was synergistic when are mixed with hexane extract; however, if the hexane extract level was higher (LD30) than the thymol level (LD10), the reaction was antagonistic. CH2Cl2 extract and thymol were more toxic than the extract or thymol alone, and EtOAc extract was synergized by thymol if the components were combined at similar levels (1:1 thymol:EtOAc extract at the LD10 or LD30). MeOH extract individually had moderate insecticidal activity, but all combinations with thymol were synergistic as binary mixtures. Isolated compounds, piperine, phenethyl cinnamamide and cinnamic acid represented synergistic, additive, and antagonistic action after combining with thymol (1:1 at the LD10 or LD30). Detoxification enzymes after exposure of insects to treatments showed isolated compounds + thymol could inhibit CE, GST and AChE reaction of S. exigua exceptional being piperine + thymol, which induced detoxification enzyme activity.

Conclusion

The synergistic activity was extract- and dose-specific. The impact on detoxification enzymes was variable and dependent on the composition of the extract and the doses of extract and thymol used in a binary mixture. In this metabolic model, the major insect compound in an extract may become detoxified, whereas a minor compound will act unimpeded, showing a lower LD50 than acting alone. This model suggests that thymol synergizes with extract components differently, which could depend on the specific metabolites in the extract and the dose applied. Such studies will help design effective insecticides based on natural plant mixtures and a synergistic compound.

Graphical abstract
The effectiveness of adjunctive measures in managing peri-implant mucositis: an umbrella review
Authors: Chuachamsai Sompol , Acharya Aneesha , Fischer Kai , Nibali Luigi , Ho Dominic , Pelekos Georgios
Published: June 2022

Objectives

The purpose of this umbrella review was to gather and summarize the data from published systematic reviews (SRs) that compared non-surgical mechanical debridement (NSMD) with and without the use of adjunctive treatments on the management of peri-implant mucositis (PIM).

Materials and methods

A protocol was developed and registered in PROSPERO (CRD42021254350) before the systematic search for the SRs. Seven electronic databases, including Cochrane Library, Embase (via Ovid), MEDLINE (via Pubmed), Proquest, Prospero, Scopus and Web of Science, were searched for published reviews. The search for unpublished and informally published reviews was further attempted in the last four databases. The methodological quality of the included reviews was assessed using AMSTAR 2.

Results

Twelve included SRs assessed clinical studies published between 2014 and 2020, including a total of seventeen primary clinical trials. All SRs summarized data from individual studies and provided a narrative conclusion regarding the effectiveness of the adjunctive treatments. Only six SRs performed a meta-analysis (MA) of additional benefits of the adjunctive therapy for PIM, with results indicating no significant difference between the different treatment modalities. The overall confidence was adjudged ranging from critically low to low using AMSTAR 2 and significant additional benefits of any adjunctive treatments in comparison with NSMD were not apparent.

Conclusion

Overall, the reviewed evidence did not support the use of adjunctive treatments for improvement of clinical outcomes in PM management as compared to NSMD alone.
Genotoxicity test of eight natural color additives in the Korean market
Authors: Do Byungkyung , Kwon Hoonjeong
Published: June 2022

Background

Various natural color additives are preferred by many consumers over synthetic color additives because they are perceived to be safer. However, most do not have sufficient toxicity data for safety assurance. Color ingredients in particular have some structures suspected of being toxic. Eight natural color additives, gardenia red, blue, and yellow; lac color; cochineal extract; beet red; Curcuma longa Linne extract (Curcuma extract); and Monascus red, currently permitted for use in Korea, were selected and subjected to genotoxicity tests. Acceptable daily intake values have not been allocated to these color additives (except for cochineal extract) due to the lack of toxicity data. We used genotoxicity testing—the bacterial reverse mutation test (Ames test), in vitro mammalian chromosomal aberration test, and in vivo alkaline comet test—for minimum safety assurance.

Results

Gardenia red and blue, cochineal extract, lac color, and beet red did not induce mutagenicity or chromosomal abnormalities. Gardenia yellow was mutagenic in the Ames test, but was not positive in the in vitro chromosomal aberration test or in vivo alkaline comet assay. Curcuma extract and Monascus red induced cytotoxicity in the Ames test at high concentrations in Salmonella typhimurium TA1537 and TA100, without showing mutagenicity. On cytotoxicity testing, Curcuma extract and Monascus red showed cytotoxicity at concentrations higher than 313 μg/ml in Chinese hamster ovary CHO-K1 cells and showed equivocal results in chromosomal aberration assay of the same cells. Curcuma extract and Monascus red produced significant increases in DNA damage at a dose of 2000 mg/kg b.w./day, and induced dose-dependent increases in % DNA in the tail and tail moment on in vivo comet assay.

Conclusions

Six out of eight food colorants did not cause genotoxicity and cytotoxicity. However, Monascus red and Curcuma extract showed definite cytotoxicity and probable genotoxicity.
Perception of the general population towards migraine in Jeddah, Saudi Arabia
Authors: Algahtani Hussein , Shirah Bader , Bamsallm Mouaz , Nejaim Kenan , Alobaidi Hussain , Alghamdi Meshal
Published: June 2022

Background

Migraine is a chronic episodic neurological disorder characterized by a myriad of neurological symptoms including multi-phase attacks of headache, photophobia, phonophobia, and dizziness. To the best of our knowledge, there are no studies conducted about the public perception and attitudes towards migraine in Saudi Arabia. This study aims to determine the public perception and attitudes towards migraine in Jeddah, Saudi Arabia. This cross-sectional study was conducted during the period between September 2019 and January 2020 in various public places including malls in Jeddah, Saudi Arabia. The study utilized a 40-item self-administered survey questionnaire divided into two sections: demographic data of the participants and perception of participants towards migraine, which consisted of three parts—knowledge towards migraine, attitudes towards migraine, and the expected behavior of migraine patients.

Results

The total number of participants was 385. Three hundred and thirty-nine of the participants (88.1%) heard about migraine before. Relatives and friends are the main source of information for 213 participants (55.3%). In gender predominance, 137 (35.6%) believed that migraine affects both genders equally. Complications of migraine headache are not known for 240 participants (62.3%). The existence of medications or methods for treating migraine is not known for 195 (50.6%). The quality of life for patients with migraine is negatively affected according to 275 (70.9%). One hundred sixty-six participants (43.1%) believe that depression and anxiety are more common in migraineurs. Two hundred forty-four (63.4%) considered migraine to cause a huge psychological and social impact. Two hundred fifteen (55.8%) do not have the knowledge to deal with migraineurs.

Conclusion

The present study demonstrated a lack of knowledge in certain aspects of migraine in Jeddah, Saudi Arabia. This study will serve as a basis for developing a health educational program aiming to increase public awareness about migraine. It will also improve the understanding of society regarding migraine, which will subsequently improve the way they interact with migraineurs and understand their difficulties. In addition, finding a trusted source for information about different kinds of medical conditions including migraine is crucial in educating the community and providing them with the most recent and correct information.
SKYSCRAPER-02: Primary results of a phase III, randomized, double-blind, placebo-controlled study of atezolizumab (atezo) + carboplatin + etoposide (CE) with or without tiragolumab (tira) in patients (pts) with untreated extensive-stage small cell lung cancer (ES-SCLC).
Authors: Rudin Charles M. , Liu Stephen V. , Lu Shun , Soo Ross A. , Hong Min Hee , Lee Jong-Seok , Bryl Maciej , Dumoulin Daphne W , Rittmeyer Achim , Chiu Chao-Hua , Ozyilkan Ozgur , Navarro Alejandro , Novello Silvia , Ozawa Yuichi , Meng Raymond , Hoang Tien , Lee Anthony , Wen Xiaohui , Huang Meilin , Reck Martin
Published: June 2022

LBA8507

Background: Atezo, in combination with CE, was the first cancer immunotherapy approved for 1L treatment of ES-SCLC. However, most pts eventually experience disease progression. TIGIT is a novel inhibitory immune checkpoint present on activated T cells and NK cells. Tira (anti-TIGIT) may synergise with other immunotherapies, such as PD-L1/PD-1 inhibitors, and further amplify the immune response to improve clinical outcomes. SKYSCRAPER-02 (NCT04256421) evaluates whether the antitumor effect and survival benefits of the combination of atezo + CE could be enhanced by adding tira in pts with ES-SCLC. Methods: Eligible pts with untreated ES-SCLC (asymptomatic treated or untreated brain metastases [BM] permitted) were randomized 1:1 to receive induction tira 600 mg IV or placebo (pbo) combined with atezo 1200 mg IV + CE for 4 x 21-day cycles followed by maintenance tira or placebo combined with atezo every 3 weeks until disease progression or loss of clinical benefit. Stratification factors include ECOG PS (0 vs 1); presence/history of BM (yes vs no); LDH (≤upper limit of normal [ULN] vs >ULN). Co-primary endpoints were investigator-assessed PFS and OS in all randomized pts without the history/presence of BM at baseline (primary analysis set [PAS]). Additional endpoints include PFS and OS in all randomized pts regardless of BM status (full analysis set [FAS]), objective response rate, duration of response, and safety. Results: A total of 490 patients were randomized (tira + atezo + CE, n=243; pbo + atezo + CE, n=247). As of 6 Feb 2022, median duration of follow-up was 13.9 months (mo); data represent final analysis for PFS and interim analysis for OS. In the PAS, no additional benefit was seen for tira + atezo + CE in PFS or OS compared with pbo + atezo + CE (Table). PFS and OS in the FAS were consistent with those observed in the PAS (Table). Grade 3/4 TRAEs occurred in 52.3% (tira + atezo + CE) and 55.7% (pbo + atezo + CE) and Grade 5 TRAEs occurred in 0.4% (tira + atezo + CE) and 2.0% (pbo + atezo + CE). TRAEs leading to any treatment discontinuation occurred in 5.0% and 5.3% with tira + atezo + CE and pbo + atezo + CE, respectively. Conclusions: The addition of tira to atezo + CE did not provide benefit over atezo + CE in pts with untreated ES-SCLC with or without BM. The combination was well tolerated, and no new safety signals were identified. The study will continue to planned final OS analysis. Clinical trial information: NCT04256421. [Table: see text]
Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases, first results from a phase III randomized controlled multicenter trial (the SCANDIUM trial).
Authors: Olofsson Bagge Roger , Nelson Axel , Shafazand Amir , All-Ericsson Charlotta , Cahlin Christian , Elander Nils , Helgadottir Hildur , Kiilgaard Jens Folke , Kinhult Sara , Ljuslinder Ingrid , Rizell Magnus , Sternby Eilard Malin , Ullenhag Gustav J. , Nilsson Jonas A , Ny Lars , Lindner Per
Published: June 2022

LBA9509

Background: Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 50% of the patients, with the liver being the most common site. The median survival for patients with liver metastases is about 6-12 months, and there are only few systemic treatment options available that moderately prolong survival. A previous trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival, compared with a historical control group consisting of the longest surviving patients in Sweden during the same time period (26 vs. 12 months). Methods: In this multicenter randomized, controlled, phase III trial, patients with previously untreated isolated liver metastasis from uveal melanoma were randomized between 2013 and 2021 to receive IHP or best alternative care (control group). The primary end point is overall survival at 24 months, but here we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS) and toxicity. Results: A total of 93 patients were randomized, with three patients in each group being excluded due to either withdrawal of consent or inappropriate enrollment, and a total of 87 patients were assigned to either IHP group (43 patients) or control group (44 patients). In the IHP group, 41 (89%) patients were treated per protocol, and in the control group, 49% of the patients were treated with chemotherapy, 39% with immunotherapy and 9% with localized treatment interventions. In an intention-to-treat analysis, the overall response rate (ORR) in the IHP group was 40% (17/43) compared to 4.5% (2/44) in the control group (p<0.0001). The median hPFS in the IHP group was 9.1 months (95% CI, 5.6 to 13.4 months), compared to 3.3 months (95% CI, 2.9 to 4.0 months) in the control group (p<0.0001). The median PFS in the IHP group was 7.4 months (95% CI, 5.2 to 11.6 months), compared to 3.3 months (95% CI, 2.9 to 3.7 months) in the control group (p<0.0001). There were 14 treatment-related serious adverse events in the IHP group, where vascular complication and infections were the most common side effects, compared to 13 in the control group where immunotherapy related side effects were most common. There was one treatment related death in the IHP group. Conclusions: Treatment with IHP resulted in superior ORR, hPFS and PFS compared to best alternative care among previously untreated patients with isolated uveal melanoma liver metastasis. Clinical trial information: NCT01785316.
Clinical, Genomic, and Transcriptomic Data Profiling of Biliary Tract Cancer Reveals Subtype-Specific Immune Signatures
Authors: Mody Kabir , Jain Prerna , El-Refai Sherif M. , Azad Nilofer S. , Zabransky Daniel J. , Baretti Marina , Shroff Rachna T. , Kelley R. Katie , El-Khouiery Anthony B. , Hockenberry Adam J. , Lau Denise , Lesinski Gregory B. , Yarchoan Mark
Published: June 2022

PURPOSE

Biliary tract cancers (BTCs) are aggressive cancers that carry a poor prognosis. An enhanced understanding of the immune landscape of anatomically and molecularly defined subsets of BTC may improve patient selection for immunotherapy and inform immune-based combination treatment strategies.

METHODS

We analyzed deidentified clinical, genomic, and transcriptomic data from the Tempus database to determine the mutational frequency and mutational clustering across the three major BTC subtypes (intrahepatic cholangiocarcinoma [IHC], extrahepatic cholangiocarcinoma, and gallbladder cancer). We subsequently determined the relationship between specific molecular alterations and anatomical subsets and features of the BTC immune microenvironment.

RESULTS

We analyzed 454 samples of BTC, of which the most commonly detected alterations were TP53 (42.5%), CDKN2A (23.4%), ARID1A (19.6%), BAP1 (15.5%), KRAS (15%), CDKN2B (14.2%), PBRM1 (11.7%), IDH1 (11.7%), TERT (8.4%), KMT2C (10.4%) and LRP1B (8.4%), and FGFR2 fusions (8.7%). Potentially actionable molecular alterations were identified in 30.5% of BTCs including 39.1% of IHC. Integrative cluster analysis revealed four distinct molecular clusters, with cluster 4 predominately associated with FGFR2 rearrangements and BAP1 mutations in IHC. Immune-related biomarkers indicative of an inflamed tumor-immune microenvironment were elevated in gallbladder cancers and in cluster 1, which was enriched for TP53, KRAS, and ATM mutations. Multiple common driver genes, including TP53, FGFR2, IDH1, TERT, BRAF, and BAP1, were individually associated with unique BTC immune microenvironments.

CONCLUSION

BTC subtypes exhibit diverse DNA alterations, RNA inflammatory signatures, and immune biomarkers. The association between specific BTC anatomical subsets, molecular alterations, and immunophenotypes highlights new opportunities for therapeutic development.
A novel route for sensing heavy metal ions in aqueous solution
Authors: Neog Ashamoni , Biswas Rajib
Published: June 2022

Heavy metal ions are some of the major aquatic pollutants which are held responsible for many ailments as well as undesired effects on flora and fauna. The World Health Organization has prescribed some permissible levels for each of the heavy metal ions. The presence of ions above permissible limits results in toxicity in the aquatic bodies as well as for other water-dependent living organisms. Therefore, it is necessary to make monitoring schemes to keep a check on the concentration of heavy metal ions. Considering this, here we report a unique route to detect heavy metal ions. Through chemical exfoliation, tungsten disulphide (WS2) nanosheets were prepared and drop casted on finger-like Cu electrodes to build the sensing unit. When the sensing unit was treated with heavy metal ions like Cu2+, Co2+, Pb2+, Hg2+, Sn2+ ions, rise in the current across the unit was observed. The concentrations of all the heavy metal ions were the same, i.e., 1 ppm. The maximum current gain was calculated for Cu2+ ions. It was found that the current gain for different ions is different in the voltage range 4–6 V and remains constant except for Cu2+ and Co2+ ions. It is believed that this novel route will pave the way for rapid and simultaneous sensing of different pervasive heavy metal ions in aqueous solutions.
Impact of a Fundamental Motor Skill Intervention on Low-Income Preschoolers’ Body Composition
Authors: Wadsworth Danielle D. , Spring Katherine E. , Johnson Jerraco L. , Carroll Alexandra V. , Sassi Julia , Suire Kameron B. , Pangelinan Melissa M. , Rudisill Mary E.
Published: June 2022

Introduction/Purpose

Fundamental motor skills (FMS)—the building blocks of play, recreation, and sport—are deficient in overweight and obese children. FMS interventions may curb increasing childhood obesity rates. This randomized control trial aimed to determine the effect of an FMS intervention on fat mass (FM), fat-free mass (FFM), and body mass index (BMI) in preschool-aged children (ages 3–5 yr) attending a low-income preschool. Researchers hypothesized that children in the intervention would have increased FFM.

Methods

Eleven preschool classes (n = 136; mean age, 4.3 yr; 74% Black) were randomly assigned to the intervention (6 classes) or control (5 classes) groups. Participants in the intervention group attended a 30-min FMS intervention two times per week for 9 months, whereas the control group simultaneously participated in outdoor-free play. FM and FFM were measured with foot-to-foot bioelectrical impedance before and after intervention. BMI was measured using height and weight.

Results

At baseline, the control group had significantly more FM (t
76
= −2.12, P = 0.04) and FFM (t
76
= −2.59, P = 0.01) than the intervention group. A mixed-effects analysis of variance examined differences in FM, FFM, and BMI with respect to group, sex, and time. Significant time by group interactions were found for FM (P = 0.05), FFM (P = 0.01), and BMI (P = 0.05). The intervention group increased FM, FFM, and BMI by 12.93%, 9.11%, and 0.75%, respectively, whereas the control group increased FM, FFM, and BMI by 23.60%, 12.75%, and 5.30%, respectively.

Conclusions

The findings of the current study suggest that an FMS intervention can delay additions of FM. It is further evident that increases in FM occurred at an alarming rate in primarily Black preschool children from a low-income center. The findings emphasize the importance of FMS in obesity prevention and measuring body composition in preschool children.
Comparison of CpG- and UpA-mediated restriction of RNA virus replication in mammalian and avian cells and investigation of potential ZAP-mediated shaping of host transcriptome compositions
Authors: Odon Valerie , Fiddaman Steven R. , Smith Adrian L. , Simmonds Peter
Published: June 2022

The ability of zinc finger antiviral protein (ZAP) to recognize and respond to RNA virus sequences with elevated frequencies of CpG dinucleotides has been proposed as a functional part of the vertebrate innate immune antiviral response. It has been further proposed that ZAP activity shapes compositions of cytoplasmic mRNA sequences to avoid self-recognition, particularly mRNAs for interferons (IFNs) and IFN-stimulated genes (ISGs) expressed during the antiviral state. We investigated whether restriction of the replication of mutants of influenza A virus (IAV) and the echovirus 7 (E7) replicon with high CpG and UpA frequencies varied in different species of mammals and birds. Cell lines from different bird orders showed substantial variability in restriction of CpG-high mutants of IAV and E7 replicons, whereas none restricted UpA-high mutants, in marked contrast to universal restriction of both mutants in mammalian cells. Dinucleotide representation in ISGs and IFN genes was compared with those of cellular transcriptomes to determine whether potential differences in inferred ZAP activity between species shaped dinucleotide compositions of highly expressed genes during the antiviral state. While mammalian type 1 IFN genes typically showed often profound suppression of CpG and UpA frequencies, there was no oversuppression of either in ISGs in any species, irrespective of their ability to restrict CpG- or UpA-high mutants. Similarly, genome sequences of mammalian and avian RNA viruses were compositionally equivalent, as were IAV strains recovered from ducks, chickens and humans. Overall, we found no evidence for host variability in inferred ZAP function shaping host or viral transcriptome compositions.
PROFILES with the CanMEDS model as a guiding framework for conveying basics in clinical medicine and physician roles to health sciences students: a qualitative study
Authors: Odermatt Florence , Schirlo Christian , Babst Reto , Gysin Stefan
Published: June 2022

Background: PROFILES (Principal Relevant Objectives and Framework for Integrative Learning and Education in Switzerland), a competency-based framework for medical students in Switzerland, was used to structure a course aiming at conveying the roles of physicians and basics in clinical medicine to health sciences students. The goal of this study was to explore how this approach was experienced and perceived by students, lecturers and experts.

Methods: For this explorative qualitative study, semi-structured interviews with seven students, four lecturers and two experts in medical education were held, and themes were identified by conducting a thematic analysis by Braun and Clarke.

Results: We identified four themes: (1) PROFILES as a guiding framework, (2) strengths and weaknesses of the course, (3) general teaching aspects and (4) potential benefits for future interprofessional collaboration. Some students initially struggled to comprehend the novel approach, but overall, the structure of the course was positively perceived by most interviewees, especially lecturers and experts.

Conclusions: PROFILES, particularly the integrated CanMEDS model, may be suitable to convey the roles and tasks of physicians and basic medical knowledge to health sciences students. Further studies are required to evaluate the effects on potential interprofessional collaboration.
The Effect of Covid 19 on Worker’s Compensation – Evidence from Gcc Countries
Authors: Mahaboob Syeda Amtul
Published: June 2022

The year 2020 has turned the world upside down with the outbreak of the disease COVID 19. It forced the companies to shift their work focus from office to work from home. Every sector of the economy got affected by the pandemic and a financial crisis was faced by almost every firm. To deal with the financial crisis, many firms have altered their compensation packages. The world of The Middle East is nowhere left behind. The firms of GCC (Gulf Cooperation Council) countries known for their attractive pay packages were forced to make modifications, adjustments, and variations to their compensation. The current paper analyzes various amendments made by firms in the Gulf Countries like Saudi Arabia, Kuwait, UAE, Qatar, Oman, and Bahrain to their compensation management system to cope with the challenges of the pandemic. It also highlights the remittances provided by the governments of these countries to tackle the situation. Analysis was done based on secondary data which includes the Gulf Health Council Report, International Labor Organization reports, Mercer Consultant Report, publication of Arab Reform Initiative, OECD (Organization for Economic Cooperation and Development) publication on MENA countries, and World Bank report (2018). The findings highlighted the turbulence experienced by employees working in gulf, as majority of GCC countries lacked in providing pay protection and job protection. It also describes to what extent the remittances provided by the government in these countries were helpful to the expatriates.
O USO DA JURIMETRIA NA ADVOCACIA PRIVADA PARA PREVISÃO DOS RESULTADOS MAIS COMUNS DE JULGAMENTOS SOBRE OBRIGAÇÕES/CONTRATOS NAS CÂMARAS DE DIREITO PRIVADO DO TRIBUNAL DE JUSTIÇA DO ESTADO DO CEARÁ
Authors: Dionísio de Andrade Mariana , Lavôr Amanda Rodrigues , Girão de Castro Pinto Eduardo Régis
Published: June 2022

O presente estudo se propõe a responder ao seguinte problema de pesquisa: Com o amparo da jurimetria, é possível identificar critérios semelhantes na fixação de danos morais pelas decisões colegiadas das Câmaras Privadas do TJCE sobre obrigações/espécies de contratos, por ser o assunto mais recorrente no tribunal da justiça estadual cearense? A utilização dessa ferramenta auxiliaria na prática da advocacia privada? Adotou-se como metodologia pesquisas bibliográficas e, no estudo de caso, utilizou-se a Metodologia de Análise das Decisões, fazendo análises quantitativas e qualitativas. Conclui-se que é possível identificar critérios semelhantes na fixação de danos morais pelas decisões das Câmaras Privadas do TJCE, por mais que a jurisprudência do tribunal estadual não seja uniforme. A incorporação da jurimetria como ferramento no dia a dia do advogado oportuniza uma visão probabilística de fenômenos de interação no contexto jurídico.
3D noise photon transfer curve
Authors: Preece Bradley L. , Haefner David P.
Published: June 2022

A photon transfer curve (PTC) is used to determine fundamental detector noise parameters such as read noise, conversion gain, and fixed pattern noise. Here, the method for determining a PTC is expanded to include 3D noise parameters. 3D noise PTC provides more insight into detector noise and is treated as the next logical step to classical PTC. However, it induces several new challenges in analyzing the results, specifically the fitting of seven, or more, variance curves compared to the one (total variance) or two (temporal and fixed pattern variance) prior. Therefore, a general measurement model is created, which provides a new method to separate out all the classical terms, such as DSNU and PRNU, but can also handle high gain cameras with a noise factor. This method is then verified using Monte Carlo simulations and applied to a commercial machine vision camera. In addition, the effects of lens vignetting and non-uniformity correction (NUC) are explored, along with a comparison of the single pixel PTC.
Fringe pattern demodulation using Zernike polynomials and al1-norm regularized extended Kalman filter
Authors: Sharma Shikha , Kulkarni Rishikesh
Published: June 2022

A novel algorithm for closed fringe demodulation for an absolute phase estimation, to the best of our knowledge, is proposed. The two-dimensional phase is represented as a weighted linear combination of a certain number of Zernike polynomials (ZPs). Essentially, the problem of phase estimation is converted into the estimation of ZP coefficients. The task of ZP coefficient estimation is performed based on a state space model. Due to the nonlinear dependence of the fringe intensity measurement model on the ZP coefficients, the extended Kalman filter (EKF) is used for the state estimation. A pseudo-measurement model is considered based on the state vector sparsity constraint to improve the convergence performance of the EKF. Simulation and experimental results are provided to demonstrate the noise robustness and the practical applicability of the proposed method.
Coherent frequency transfer with < 5*10−21 stability via a multi-branch comb with noise cancellation
Authors: Li Peng , Rolland Antoine , Jiang Jie , Fermann Martin E.
Published: June 2022

We demonstrate a multi-branch frequency comb for spectral purity transfer incorporating hardware enabled noise cancellation based on a cw noise transfer laser. We verify coherent frequency transfer at stabilities ≈ 2×10−18 in 1 second and < 5×10−21 in 10,000 seconds without any reference cavity.
Characterizing propagation-dependent spatial entanglement for structured laser beams generated by an astigmatic mode converter
Authors: Yu Y. T. , Hsieh M. X. , Liang H. C. , Chen Y. F.
Published: June 2022

The propagation-dependent spatial entanglement for the structured laser beams generated by an arbitrary incident Hermite–Gaussian (HG) mode passing through an astigmatic mode converter (AMC) is theoretically explored. The structured output beams are analytically decomposed into the expansion of HG modes for any given rotation angle of the AMC. Based on the Schmidt decomposition, the propagation-dependent spatial entanglements of the structured output modes are quantified with the von Neumann entropy. To manifest the propagation-dependent entropy, the probability distribution of the expanded HG modes in the structured output beam is quantitatively analyzed.
Physics-driven deep learning enables temporal compressive coherent diffraction imaging
Authors: Chen Ziyang , Zheng Siming , Tong Zhishen , Yuan Xin
Published: June 2022

Coherent diffraction imaging (CDI), as a lensless imaging technique, can achieve a high-resolution image with intensity and phase information from a diffraction pattern. To capture high-speed and high-spatial-resolution scenes, we propose a temporal compressive CDI system. A two-step algorithm using physics-driven deep-learning networks is developed for multi-frame spectra reconstruction and phase retrieval. Experimental results demonstrate that our system can reconstruct up to eight frames from a snapshot measurement. Our results offer the potential to visualize the dynamic process of molecules with large fields of view and high spatial and temporal resolutions.
Zum Erbbauzinssatz: Das Rätsel um die Marktgerechtigkeit
Authors: Löhr Dirk
Published: June 2022

Der Erbbauzins ist bei kommunalen Erbbaurechten sowohl eine zentrale Stellgröße für die Wirtschaftlichkeit als auch von kommunalwirtschafts- und beihilferechtlicher Relevanz. Er wird zumeist ermittelt, indem ein geeigneter Erbbauzinssatz auf den Bodenwert angelegt wird. Der Erbbauzinssatz sollte dabei marktgerecht sein. Sowohl die Ableitung des Erbbauzinssatzes aus dem Primärmarkt (erstmalige Ausgabe von Erbbaurechten) wie aus dem Sekundärmarkt (Weiterverkäufe) ist aber zumindest bei Erbbaurechten für Mehrfamilienhäuser derzeit kaum sinnvoll zu diesem Zwecke durchzuführen. Auch der Liegenschaftszinssatz ist ungeeignet, da er aus einem Modell für Volleigentum mit einer vollkommen anderen Risiko-/Rendite-Konstellation abgeleitet wird. Daher wird für eine stärkere Anwendung ökonomisch basierter Verfahren plädiert und hierbei ein kapitalmarktorientiertes Mark-to-Model-Verfahren dargestellt. Erste überschlägige Ermittlungen legen zudem die Orientierung an langfristigen Baufinanzierungssätzen als Daumenregel nahe. Regelmäßig dürften von Kommunen für die Ermittlung von marktgerechten Erbbauzinssätzen öffentlich bestellte und vereidigte oder zertifizierte Grundstückssachverständige betraut werden, denen die betreffenden Verfahren jedoch oftmals fremd sind. Auch stellt sich die Frage nach der Zulässigkeit, da sie sich als Best Practice-Verfahren bislang nicht etabliert haben. Daher wäre dem Gesetz- bzw. Verordnungsgeber anzuraten, die Ermittlung marktgerechter Erbbauzinssätze ausdrücklich zu regeln und dabei jenseits von Mark-to-Market-Verfahren weitere geeignete ökonomisch gestützte Methoden wie auch empirisch abgesicherte „Daumenregeln“ zuzulassen.
OLA-1, an Obg-like ATPase, integrates hunger with temperature information in sensory neurons in C. elegans
Authors: Aoki Ichiro , Jurado Paola , Nawa Kanji , Kondo Rumi , Yamashiro Riku , Matsuyama Hironori J. , Ferrer Isidre , Nakano Shunji , Mori Ikue
Published: June 2022

Animals detect changes in both their environment and their internal state and modify their behavior accordingly. Yet, it remains largely to be clarified how information of environment and internal state is integrated and how such integrated information modifies behavior. Well-fedC.elegansmigrates to past cultivation temperature on a thermal gradient, which is disrupted when animals are starved. We recently reported that the neuronal activities synchronize between a thermosensory neuron AFD and an interneuron AIY, which is directly downstream of AFD, in well-fed animals, while this synchrony is disrupted in starved animals. However, it remained to be determined whether the disruption of the synchrony is derived from modulation of the transmitter release from AFD or from the modification of reception or signal transduction in AIY. By performing forward genetics on a transition of thermotaxis behavior along starvation, we revealed that OLA-1, an Obg-like ATPase, functions in AFD to promote disruption of AFD-AIY synchrony and behavioral transition. Our results suggest that the information of hunger is delivered to the AFD thermosensory neuron and gates transmitter release from AFD to disrupt thermotaxis, thereby shedding light onto a mechanism for the integration of environmental and internal state to modulate behavior.
Large gains in schooling and income are possible from minimizing adverse birth outcomes in 121 low- and middle-income countries: A modelling study
Authors: Blakstad Mia M. , Perumal Nandita , Bliznashka Lilia , Lambiris Mark J. , Fink Günther , Danaei Goodarz , Sudfeld Christopher R.
Published: June 2022

While the global contributions of adverse birth outcomes to child morbidity and mortality is relatively well documented, the potential long-term schooling and economic consequences of adverse birth outcomes has not been estimated. We sought to quantify the potential schooling and lifetime income gains associated with reducing the excess prevalence of adverse birth outcomes in 121 low- and middle-income countries. We used a linear deterministic model to estimate the potential gains in schooling and lifetime income that may be achieved by attaining theoretical minimum prevalence of low birthweight, preterm birth and small-for-gestational age births at the national, regional, and global levels. We estimated that potential total gains across the 121 countries from reducing low birthweight to the theoretical minimum were 20.3 million school years (95% CI: 6.0,34.8) and US$ 68.8 billion (95% CI: 20.3,117.9) in lifetime income gains per birth cohort. As for preterm birth, we estimated gains of 9.8 million school years (95% CI: 1.5,18.4) and US$ 41.9 billion (95% CI: 6.1,80.9) in lifetime income. The potential gains from small-for-gestational age were 39.5 million (95% CI: 19.1,60.3) school years and US$113.6 billion (95% CI: 55.5,174.2) in lifetime income gained. In summary, reducing the excess prevalence of low birthweight, preterm birth or small-for-gestational age births in low- and middle-income countries may lead to substantial long-term human capital gains in addition to benefits on child mortality, growth, and development as well as on risk of non-communicable diseases in adults and other consequences across the life course.
Understanding antimicrobial use in subsistence farmers in Chikwawa District Malawi, implications for public awareness campaigns
Authors: MacPherson Eleanor E. , Reynolds Joanna , Sanudi Esnart , Nkaombe Alexander , Mankhomwa John , Dixon Justin , Chandler Clare I. R.
Published: June 2022

Drug resistant infections are increasing across the world and urgent action is required to preserve current classes of antibiotics. Antibiotic use practices in low-and-middle-income countries have gained international attention, especially as antibiotics are often accessed beyond the formal health system. Public awareness campaigns have gained popularity, often conceptualising antimicrobial resistance (AMR) as a problem of excess, precipitated by irrational behaviour. Insufficient attention has been paid to people’s lived experiences of accessing medicines in low-income contexts. In Chikwawa District, Malawi, a place of extreme scarcity, our study aimed to understand the care and medicine use practices of households dependent on subsistence farming. Adopting an anthropological approach, we undertook medicine interviews (100), ethnographic fieldwork (six-month period) and key informant interviews (33) with a range of participants in two villages in rural Chikwawa. The most frequently used drugs were cotrimoxazole and amoxicillin, not considered to be of critical importance to human health. Participants recognised that keeping, sharing, and buying medicines informally was not the “right thing.” However, they described using antibiotics and other medicines in these ways due to conditions of extreme precarity, the costs and limitations of seeking formal care in the public sector, and the inevitability of future illness. Our findings emphasise the need in contexts of extreme scarcity to equip policy actors with interventions to address AMR through strengthening health systems, rather than public awareness campaigns that foreground overuse and the dangers of using antibiotics beyond the formal sector.
Will the use of industrial robots promote transformation of export trade modes? Empirical evidence from China
Authors: Wang Dongmei , Li Guangqin
Published: June 2022

Based on China’s Industrial Robot and Customs data from 2006 to 2019, this paper conducts an empirical investigation into the impact of industrial robot usage on export trade structures and its working mechanism with the popularization of industrial robots and the expansion of export trade in China. It finds that the use of industrial robots has significantly increased the proportion of general trade, reduced that of processing trade and promoted the transformation from processing-trade into general-trade, or the impact mechanism of industrial robots on export trade structure. After adopting such two methods as lag phase and tool variables to address potential endogenous problems, the results continue to be valid. In addition, the paper also discussed the regional heterogeneity effect of industrial robot trade transformation. Such evidence provides a new perspective for developing countries to explain the transformation of their export trade and are of high significance in optimizing the structure of trade patterns and promoting the transformation of export trade.
Pattern of tamoxifen-induced Tie2 deletion in endothelial cells in mature blood vessels using endo SCL-Cre-ERT transgenic mice
Authors: Zwiers Peter J. , Jongman Rianne M. , Kuiper Timara , Moser Jill , Stan Radu V. , Göthert Joachim R. , van Meurs Matijs , Popa Eliane R. , Molema Grietje
Published: June 2022

Tyrosine-protein kinase receptor Tie2, also known as Tunica interna Endothelial cell Kinase or TEK plays a prominent role in endothelial responses to angiogenic and inflammatory stimuli. Here we generated a novel inducible Tie2 knockout mouse model, which targets mature (micro)vascular endothelium, enabling the study of the organ-specific contribution of Tie2 to these responses. Mice with floxed Tie2 exon 9 alleles (Tie2floxed/floxed) were crossed with end-SCL-Cre-ERT transgenic mice, generating offspring in which Tie2 exon 9 is deleted in the endothelial compartment upon tamoxifen-induced activation of Cre-recombinase (Tie2ΔE9). Successful deletion of Tie2 exon 9 in kidney, lung, heart, aorta, and liver, was accompanied by a heterogeneous, organ-dependent reduction in Tie2 mRNA and protein expression. Microvascular compartment-specific reduction in Tie2 mRNA and protein occurred in arterioles of all studied organs, in renal glomeruli, and in lung capillaries. In kidney, lung, and heart, reduced Tie2 expression was accompanied by a reduction in Tie1 mRNA expression. The heterogeneous, organ- and microvascular compartment-dependent knockout pattern of Tie2 in the Tie2floxed/floxed;end-SCL-Cre-ERT mouse model suggests that future studies using similar knockout strategies should include a meticulous analysis of the knockout extent of the gene of interest, prior to studying its role in pathological conditions, so that proper conclusions can be drawn.