bluuebunny/crossref_metadata_2025 huggingface dataset:
The associations between plasma soluble Trem1 and neurological diseases: a Mendelian randomization study
Authors: Shi Xiaolei , Wei Tao , Hu Yachun , Wang Meng , Tang Yi
Published: September 2022

Background

Triggering receptor expressed on myeloid cell 1 (Trem1) is an important regulator of cellular inflammatory responses. Neuroinflammation is a common thread across various neurological diseases. Soluble Trem1 (sTrem1) in plasma is associated with the development of central nervous system disorders. However, the extent of any causative effects of plasma sTrem1 on the risk of these disorders is still unclear.

Method

Genetic variants for plasma sTrem1 levels were selected as instrumental variables. Summary-level statistics of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), epilepsy, cerebrovascular diseases, and migraine were collected from genome-wide association studies (GWASs). Whether plasma sTrem1 was causally associated with neurological disorders was assessed using a two-sample Mendelian randomization (MR) analysis, with false discovery rate (FDR)-adjusted methods applied.

Results

We inferred suggestive association of higher plasma sTrem1 with the risk of AD (odds ratio [OR] per one standard deviation [SD] increase = 1.064, 95% CI 1.012–1.119, P = 0.014, PFDR = 0.056). Moreover, there was significant association between plasma sTrem1 level and the risk of epilepsy (OR per one SD increase = 1.044, 95% CI 1.016–1.072, P = 0.002, PFDR = 0.032), with a modest statistical power of 41%. Null associations were found for plasma sTrem1 with other neurological diseases and their subtypes.

Conclusions

Taken together, this study indicates suggestive association between plasma sTrem1 and AD. Moreover, higher plasma sTrem1 was associated with the increased risk of epilepsy. The findings support the hypothesis that sTrem1 may be a vital element on the causal pathway to AD and epilepsy.
Seasonal epidemiological and clinical characteristics of pediatric patients with human parainfluenza virus infection by serotype: a retrospective study
Authors: Han Ji Yoon , Suh Woosuck , Han Seung Beom
Published: September 2022

Background

The development of the polymerase chain reaction (PCR) test promoted the evaluation of the epidemiological and clinical characteristics of human parainfluenza virus (HPIV) type 4, which has been rarely studied using conventional diagnostic methods. This study aimed to determine the seasonal epidemiological and clinical characteristics of all four HPIV serotypes (HPIV-1, HPIV-2, HPIV-3, and HPIV-4) during the era of PCR testing.

Methods

The medical records of hospitalized pediatric patients diagnosed with HPIV infections by a multiplex PCR test between 2015 and 2021 were retrospectively reviewed to determine the seasonal distributions of each HPIV serotype. For patients with a single HPIV infection, the clinical characteristics of each HPIV serotype were evaluated and compared with one another.

Results

Among the 514 cases of HPIV infection, HPIV-1, HPIV-2, HPIV-3, and HPIV-4 were identified in 27.2%, 11.9%, 42.6%, and 18.3% of cases, respectively. HPIV-3 was most prevalent in spring, and the other three serotypes were most prevalent in autumn. For patients with a single HPIV infection, those infected by HPIV-1 and HPIV-3 were younger than those infected by HPIV-2 and HPIV-4 (P < 0.001). Croup and lower respiratory tract infection (LRI) were most frequently diagnosed in patients infected by HPIV-1 (P < 0.001) and HPIV-4 (P = 0.002), respectively. During 2020–2021, HPIV-3 was most prevalent in autumn and caused fewer LRIs (P = 0.009) and more seizures (P < 0.001) than during 2015–2019.

Conclusions

Each HPIV serotype exhibited a distinct seasonal predominance, and some differences in the clinical characteristics of the HPIV serotypes were observed. HPIV-4 acted as an important cause of LRI. Considering the recent changes in the epidemiological and clinical characteristics of HPIV-3, more time-series analyses should be conducted.
Understanding the socioeconomic costs of dystrophic epidermolysis bullosa in Europe: a costing and health-related quality of life study
Authors: Angelis A. , Mellerio J. E. , Kanavos P.
Published: September 2022

Background

Dystrophic epidermolysis bullosa (EB) is a family of rare genetic dermatological conditions. Recent evidence indicated that in addition to its detrimental implications on patient health-related quality of life (HRQoL), there are substantial socioeconomic cost implications, especially regarding direct non-medical costs. This study aims to understand the burden of dystrophic EB (DEB) in Europe, using a primary EB patient-level dataset.

Methods

A bottom-up, cross-sectional, study design was adopted for non-institutionalised patients diagnosed with EB who received outpatient care across EU5 countries: France, Germany, Italy, Spain, and the United Kingdom. A prevalence-based approach was used to estimate resource utilisation from a societal perspective, including direct (medical and non-medical) and indirect costs for patients and caregivers. Patient and caregiver outcomes were obtained using the EQ-5D questionnaire.

Results

A sample of 91 DEB patients was analysed. Overall, average EU5 annual cost per patient was estimated at €53,359, ranging from €18,783 (France) to €79,405 (Germany). Average EU5 annual direct medical costs were estimated at €8357 (15.7% of total), ranging from €5658 (France) to €12,576 (Germany); average direct non-medical costs were estimated at €41,353 (77.5% of total), ranging from €11,961 (France) to €57,000 (Germany); and average indirect costs were estimated at €3649 (6.8% of total), ranging from €1025 (Italy) to €9930 (United Kingdom). Costs varied across patients with different disability but also between children and adults. The mean EQ-5D index score for adult DEB patients ranged between 0.304 (United Kingdom) and 0.541 (Germany), with an EU5 average of 0.456, whereas the mean EQ-5D visual analogue scale score ranged between 47.5 (Germany) and 70.0 (France), with an EU5 average of 61.9. Limitations included potential patient selection bias, recall bias, and exclusion of bandaging and related costs.

Conclusions

The study revealed a substantial socioeconomic burden for DEB in Europe, attributable mostly to high direct non-medical costs, with the majority of patients requiring support from caregivers at home. Compared to the average economic burden of the overall EB patient population, costs for DEB patients are higher across all components of direct medical, direct non-medical and indirect costs.
A novel loss-of-function mutation of the voltage-gated potassium channel Kv10.2 involved in epilepsy and autism
Authors: Galán-Vidal Jesús , Socuéllamos Paula G. , Baena-Nuevo María , Contreras Lizbeth , González Teresa , Pérez-Poyato María S. , Valenzuela Carmen , González-Lamuño Domingo , Gandarillas Alberto
Published: September 2022

Background

Novel developmental mutations associated with disease are a continuous challenge in medicine. Clinical consequences caused by these mutations include neuron and cognitive alterations that can lead to epilepsy or autism spectrum disorders. Often, it is difficult to identify the physiological defects and the appropriate treatments.

Results

We have isolated and cultured primary cells from the skin of a patient with combined epilepsy and autism syndrome. A mutation in the potassium channel protein Kv10.2 was identified. We have characterised the alteration of the mutant channel and found that it causes loss of function (LOF). Primary cells from the skin displayed a very striking growth defect and increased differentiation. In vitro treatment with various carbonic anhydrase inhibitors with various degrees of specificity for potassium channels, (Brinzolamide, Acetazolamide, Retigabine) restored the activation capacity of the mutated channel. Interestingly, the drugs also recovered in vitro the expansion capacity of the mutated skin cells. Furthermore, treatment with Acetazolamide clearly improved the patient regarding epilepsy and cognitive skills. When the treatment was temporarily halted the syndrome worsened again.

Conclusions

By in vitro studying primary cells from the patient and the activation capacity of the mutated protein, we could first, find a readout for the cellular defects and second, test pharmaceutical treatments that proved to be beneficial. The results show the involvement of a novel LOF mutation of a Potassium channel in autism syndrome with epilepsy and the great potential of in vitro cultures of primary cells in personalised medicine of rare diseases.
Behçet’s disease in Wales: an epidemiological description of national surveillance data
Authors: Ashman Annie , Tucker David , Williams Ceri , Davies Llion
Published: September 2022

Objectives

Behçet’s disease is a rare, chronic, incurable, multisystemic disease. It causes significant morbidity, with patients experiencing symptoms including mucous membrane ulcers, and joint pain and swelling. It is an important cause of avoidable blindness due to ocular involvement. The aetiology is unknown. The aims were to identify population prevalence of Behçet’s disease in Wales in comparison to other endemic and non-endemic regions, and provide an epidemiological profile of a case series of adult patients. This is the first analysis of data from the Adult Rare Diseases Surveillance Registry for Wales, established in 2020 as part of the COVID-19 pandemic response.

Results

Between 1995 and 2020, 347 adults and 5 children were recorded in Wales with a diagnosis of Behçet’s disease. Population prevalence was calculated as 11.1 per 100,000 population. Of the adult cases, 76.9% were female, and 6.6% died before the end of the study period. When comparing genders, there were no statistically significant differences in age at diagnosis, mortality or socioeconomic status. There was no evidence that the age at which cases were diagnosed had changed over time. Survival analyses showed no significant differences in durations of survival between genders or individuals residing in different WIMD 2019 quintiles. Age at diagnosis was the only factor significantly and independently associated with poorer durations of survival (p < 0.001).
Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies
Authors: Dugué Pierre-Antoine , Bodelon Clara , Chung Felicia F. , Brewer Hannah R. , Ambatipudi Srikant , Sampson Joshua N. , Cuenin Cyrille , Chajès Veronique , Romieu Isabelle , Fiorito Giovanni , Sacerdote Carlotta , Krogh Vittorio , Panico Salvatore , Tumino Rosario , Vineis Paolo , Polidoro Silvia , Baglietto Laura , English Dallas , Severi Gianluca , Giles Graham G. , Milne Roger L. , Herceg Zdenko , Garcia-Closas Montserrat , Flanagan James M. , Southey Melissa C.
Published: September 2022

Background

DNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including cancer. Here we aimed to study epigenetic measures of aging and lifestyle-related factors in association with risk of breast cancer.

Methods

Using data from four prospective case–control studies nested in three cohorts of European ancestry participants, including a total of 1,655 breast cancer cases, we calculated three methylation-based measures of lifestyle factors (body mass index [BMI], tobacco smoking and alcohol consumption) and seven measures of epigenetic aging (Horvath-based, Hannum-based, PhenoAge and GrimAge). All measures were regression-adjusted for their respective risk factors and expressed per standard deviation (SD). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional or unconditional logistic regression and pooled using fixed-effects meta-analysis. Subgroup analyses were conducted by age at blood draw, time from blood sample to diagnosis, oestrogen receptor-positivity status and tumour stage.

Results

None of the measures of epigenetic aging were associated with risk of breast cancer in the pooled analysis: Horvath ‘age acceleration’ (AA): OR per SD = 1.02, 95%CI: 0.95–1.10; AA-Hannum: OR = 1.03, 95%CI:0.95–1.12; PhenoAge: OR = 1.01, 95%CI: 0.94–1.09 and GrimAge: OR = 1.03, 95%CI: 0.94–1.12, in models adjusting for white blood cell proportions, body mass index, smoking and alcohol consumption. The BMI-adjusted predictor of BMI was associated with breast cancer risk, OR per SD = 1.09, 95%CI: 1.01–1.17. The results for the alcohol and smoking methylation-based predictors were consistent with a null association. Risk did not appear to substantially vary by age at blood draw, time to diagnosis or tumour characteristics.

Conclusion

We found no evidence that methylation-based measures of aging, smoking or alcohol consumption were associated with risk of breast cancer. A methylation-based marker of BMI was associated with risk and may provide insights into the underlying associations between BMI and breast cancer.
The current status and future prospects for molecular imaging-guided precision surgery
Authors: Boekestijn Imke , van Oosterom Matthias N. , Dell’Oglio Paolo , van Velden Floris H. P. , Pool Martin , Maurer Tobias , Rietbergen Daphne D. D. , Buckle Tessa , van Leeuwen Fijs W. B.
Published: September 2022

Molecular imaging technologies are increasingly used to diagnose, monitor, and guide treatment of i.e., cancer. In this review, the current status and future prospects of the use of molecular imaging as an instrument to help realize precision surgery is addressed with focus on the main components that form the conceptual basis of intraoperative molecular imaging. Paramount for successful interventions is the relevance and accessibility of surgical targets. In addition, selection of the correct combination of imaging agents and modalities is critical to visualize both microscopic and bulk disease sites with high affinity and specificity. In this context developments within engineering/imaging physics continue to drive the growth of image-guided surgery. Particularly important herein is enhancement of sensitivity through improved contrast and spatial resolution, features that are critical if sites of cancer involvement are not to be overlooked during surgery. By facilitating the connection between surgical planning and surgical execution, digital surgery technologies such as computer-aided visualization nicely complement these technologies. The complexity of image guidance, combined with the plurality of technologies that are becoming available, also drives the need for evaluation mechanisms that can objectively score the impact that technologies exert on the performance of healthcare professionals and outcome improvement for patients.
CSF rhinorrhea: non-contrast CT, contrast-enhanced CT cisternography or combined?
Authors: Hablas Lina Tarek , Ammar Alshimaa Magdy , Elnagar Rehab Mohamed
Published: September 2022

Background

Radiologic diagnosis of CSF leaks is challenging. We evaluated the diagnostic value of non-contrast CT and contrast-enhanced CT cisternography in identifying the presence of CSF rhinorrhea and site of leak as well as comparing them to surgical data and/or clinical follow-up.

Results

Fifty patients (20 males and 30 females) were included in our study with age ranging from 19 to 67 years. 76% of cases had spontaneous CSF rhinorrhea. Cribriform plate defect was the most common site of CSF leak, accounting for about 50% of cases. The highest sensitivity, specificity, PPV and NPV for diagnosis of CSF rhinorrhea were observed with the combined NCCT and CECTC with values 87%, 100%, 100% and 67%, respectively.

Conclusion

Accurate surgical planning and successful dural repair requires accurate localization of the dural and osseous defects. CT cisternography which already involves pre-cisternography non-contrast images holds great sensitivity in detection of the exact defect site together with confirmation of the CSF leak.
Acquired Genomic Alterations on First-Line Chemotherapy With Cetuximab in Advanced Colorectal Cancer: Circulating Tumor DNA Analysis of the CALGB/SWOG-80405 Trial (Alliance)
Authors: Raghav Kanwal , Ou Fang-Shu , Venook Alan P. , Innocenti Federico , Sun Ryan , Lenz Heinz-Josef , Kopetz Scott
Published: September 2022

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co‐primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

Acquired genomic alterations (Acq-GAs), specifically RAS, BRAF, and EGFR-ectodomain mutations and ERBB2 and MET amplifications, are recognized as major mechanisms of resistance to later-line anti–EGFR-antibody therapy in metastatic colorectal cancer (mCRC). However, data regarding emergence of these Acq-GAs under the selective pressure of first-line anti–EGFR-chemotherapy are lacking. We performed next-generation sequencing (Guardant360) on circulating tumor DNA obtained from paired plasma samples (pretreatment and postprogression) from the CALGB/SWOG-80405 trial, which randomly assigned patients with mCRC between first-line chemotherapy with cetuximab (anti–EGFR-chemotherapy) or bevacizumab (anti–VEGF-chemotherapy). The primary objective was to determine the prevalence of Acq-GAs on anti–EGFR-chemotherapy and compare this to the prevalence with anti–VEGF-chemotherapy on trial and pooled estimates (N = 292) seen with later-line anti–EGFR-antibody therapy as reported in the literature. Among the 61 patients on anti–EGFR-chemotherapy, only four (6.6%) developed ≥ 1 Acq-GAs of interest compared with 10.1% (7) on anti–VEGF-chemotherapy (odds ratio, 0.62; 95% CI, 0.20 to 2.11) and 62.0% on anti–EGFR-antibody therapy in later lines (odds ratio, 0.09; 95% CI, 0.03 to 0.23). Acq-GAs, classically associated with anti–EGFR-antibody resistance in later lines ( RAS, BRAF, and EGFR-ectodomain mutations; ERBB2 and MET amplifications), were rare with up-front use of anti–EGFR-chemotherapy indicating divergent resistance mechanisms. These findings have critical translational relevance to timing and value of circulating tumor DNA–guided anti-EGFR rechallenge in patients with mCRC, especially those treated with anti-EGFR therapy upfront.
Consensus Recommendations for the Use of Automated Insulin Delivery Technologies in Clinical Practice
Authors: Phillip Moshe , Nimri Revital , Bergenstal Richard M , Barnard-Kelly Katharine , Danne Thomas , Hovorka Roman , Kovatchev Boris P , Messer Laurel H , Parkin Christopher G , Ambler-Osborn Louise , Amiel Stephanie A , Bally Lia , Beck Roy W , Biester Sarah , Biester Torben , Blanchette Julia E , Bosi Emanuele , Boughton Charlotte K , Breton Marc D , Brown Sue A , Buckingham Bruce A , Cai Albert , Carlson Anders L , Castle Jessica R , Choudhary Pratik , Close Kelly L , Cobelli Claudio , Criego Amy B , Davis Elizabeth , de Beaufort Carine , de Bock Martin I , DeSalvo Daniel J , DeVries J Hans , Dovc Klemen , Doyle Francis J , Ekhlaspour Laya , Shvalb Naama Fisch , Forlenza Gregory P , Gallen Geraldine , Garg Satish K , Gershenoff Dana C , Gonder-Frederick Linda A , Haidar Ahmad , Hartnell Sara , Heinemann Lutz , Heller Simon , Hirsch Irl B , Hood Korey K , Isaacs Diana , Klonoff David C , Kordonouri Olga , Kowalski Aaron , Laffel Lori , Lawton Julia , Lal Rayhan A , Leelarathna Lalantha , Maahs David M , Murphy Helen R , Nørgaard Kirsten , O’Neal David , Oser Sean , Oser Tamara , Renard Eric , Riddell Michael C , Rodbard David , Russell Steven J , Schatz Desmond A , Shah Viral N , Sherr Jennifer L , Simonson Gregg D , Wadwa R Paul , Ward Candice , Weinzimer Stuart A , Wilmot Emma G , Battelino Tadej
Published: September 2022

The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage.
Takotsubo Syndrome Secondary to Pulmonary Bronchoscopy
Authors: Marchi Blatt Camila , Vianna Magalhães Rafaela , Soares Cruz João Vitor , Nunes Larissa , Avelino Frandoloso Gibran , Savogin Andraus Gabriel , Saray Marchesini Stival Rebecca
Published: September 2022

Takotsubo syndrome is known for its association with psychological stress factors. Rarely, it is associated with invasive procedures. We present a case of Takotsubo induced by bronchoscopy, a procedure with a low rate of complications.
DELİ DUMRUL HİKÂYESİ’NDE VE EVERYMAN’DE ÖLÜM TEMSİLLERİ
Authors: AKSÜT ÇOBANOĞLU Seda
Published: September 2022

Death is a reality of human life that everybody will experience sooner or later. As a universal concept, the reality and fear of death can be observed in many literary works. The Story of Deli Dumrul Son of Duha Kodja and Everyman are among the literary works in which death is included as a cultural representation. The Story of Deli Dumrul is one of the stories from the Book of Dede Korkut and tells the adventures of Deli Dumrul, who challenges Azrael. Everyman is an allegorical English morality play, in which the protagonist Everyman’s journey of death and reckoning process are told. Both of the texts belong to medieval times, and the concept of death is not handled as just a literary theme but also a fact of life in each. In the Story of Deli Dumrul, as a result of his challenge to Azrael, Deli Dumrul is punished by God via the decision of his death. In Everyman, the sinful character Everyman’s process of pre-death is depicted as a spiritual journey on the basis of the Christian religion. Each text deals with the concept of death in a different cultural context. Hence, they each represent death in accordance with their cultural features. In each text, death is personified and included as a character, namely Azrael and Death. The primary objective of this study is to discuss the way death is portrayed as a character in the light of the cultural milieu in these texts. For this objective, the way death is represented in relation to other characters is tried to be examined and analyzed in a comparative way with regard to the texts’ sociocultural and religious background. The arguments are discussed with relevant references to the literary texts mentioned. In the study, representations of death are investigated in terms of three aspects: death as God’s wrath; death as a threatening and disturbing character; death as a trigger in the protagonists’ awakening/rationalization process. Thus, representations of death in the mentioned texts are discussed in relation to God’s and the protagonists’ attitudes and actions. This study also investigates how cultural patterns are reflected in each text on the basis of representations of death. Death, in the form of a character in both of the texts, functions as a trigger by which the protagonists go through a maturation process. The fact that death’s being a trigger in the maturation process of the protagonists is common in both texts confirms that facing the reality of death has a didactic effect/function and that the representations of death in literary texts could have an educational aspect.
Design and experimental study of a fiber Bragg grating strain sensor with enhanced sensitivity
Authors: Pan Jianjun , Hou Wei , Wang Liangying , Zou Zisong , Xiao Fan
Published: September 2022

A novel high-sensitivity fiber Bragg grating (FBG) strain sensor is reported, to the best of our knowledge. The sensitivity of the sensor is improved by fixing the FBG on an elastic substrate with a sensitization function. The sensitization principle of the designed sensor is introduced, and the mathematical model of the sensor is established. In the static and dynamic experiments of the sensor, the effect of adhesive between the sensor and the measured structure on the sensitivity of the FBG strain sensor is experimentally investigated. The experimental results show that the adhesive with high shear strength is beneficial to the realization of a high-sensitivity sensor. The sensor fixed with planting bar glue can achieve a sensitivity of 9.42 pm/µ

ε

, a repeatability error of 4.79%, and a hysteresis error of 3.36%, which is consistent with theoretical and simulation results. The designed high-sensitivity strain sensor has a simple structure, small size, and convenient installation, so it has a good application prospect in micro-strain monitoring.
Heterogeneities of zebrafish vasculature development studied by a high throughput light-sheet flow imaging system
Authors: Yang Guang , Wang Linbo , Qin Xiaofei , Chen Xiaohu , Liang Yong , Jin Xin , Chen Chong , Zhang Wenjuan , Pan Weijun , Li Hui
Published: September 2022

Zebrafish is one of the ideal model animals to study the structural and functional heterogeneities in development. However, the lack of high throughput 3D imaging techniques has limited studies to only a few samples, despite zebrafish spawning tens of embryos at once. Here, we report a light-sheet flow imaging system (LS-FIS) based on light-sheet illumination and a continuous flow imager. LS-FIS enables whole-larva 3D imaging of tens of samples within half an hour. The high throughput 3D imaging capability of LS-FIS was demonstrated with the developmental study of the zebrafish vasculature from 3 to 9 days post-fertilization. Statistical analysis shows significant variances in trunk vessel development but less in hyaloid vessel development.
Microwave photonic multiform microwave frequency shift keying signal generator
Authors: Feng Kuisheng , Li Na , Wang Guodong , Xiao Jin , Jiang Wei
Published: September 2022

A photonic approach to realizing multiform microwave frequency shift keying (FSK) signal generation is proposed and demonstrated. In the scheme, a commercial dual-polarization quadrature phase shift keying modulator (DP-QPSKM) is employed to generate two orthogonally-polarized signals containing specific optical sidebands, and a subsequent Sagnac loop structure govern the interference results of these two signals. From a theoretical analysis, when the modulators are properly biased, microwave FSK signal with fixed double relationship or flexibly tunable subcarrier frequencies can be obtained, and high frequency multiplication can be realized in the meantime. Furthermore, a photonic-optimized coherent demodulation structure is designed to recover the binary coding data, which can effectively avoid the electronic bottleneck. Simulation has been performed to investigate the mechanism and the discussions about the robustness to non-ideal parameters including DC bias, phase shift and polarization angle are also given. In the proof-of-concept experiment, microwave FSK signal with subcarrier frequencies of 2/4, 2.2/3.8, 2.4/3.6, 2.6/3.4, 2.8/3.2 GHz are generated, and the correct binary coding data is successfully recovered with the aid of simulation platform. The simulation and experimental results can verify the feasibility of the proposed multiform microwave FSK signal generator, which may find applications in modern radar and communication systems.
Quantitative protein sensing with germanium THz-antennas manufactured using CMOS processes
Authors: Hardt Elena , Chavarin Carlos Alvarado , Gruessing Soenke , Flesch Julia , Skibitzki Oliver , Spirito Davide , Vita Gian Marco , Simone Giovanna De , Masi Alessandra di , You Changjiang , Witzigmann Bernd , Piehler Jacob , Capellini Giovanni
Published: September 2022

The development of a CMOS manufactured THz sensing platform could enable the integration of state-of-the-art sensing principles with the mixed signal electronics ecosystem in small footprint, low-cost devices. To this aim, in this work we demonstrate a label-free protein sensing platform using highly doped germanium plasmonic antennas realized on Si and SOI substrates and operating in the THz range of the electromagnetic spectrum. The antenna response to different concentrations of BSA shows in both cases a linear response with saturation above 20 mg/mL. Ge antennas on SOI substrates feature a two-fold sensitivity as compared to conventional Si substrates, reaching a value of 6 GHz/(mg/mL), which is four-fold what reported using metal-based metamaterials. We believe that this result could pave the way to a low-cost lab-on-a-chip biosensing platform.
M-TUBE enables large-volume bacterial gene delivery using a high-throughput microfluidic electroporation platform
Authors: Huang Po-Hsun , Chen Sijie , Shiver Anthony L. , Culver Rebecca Neal , Huang Kerwyn Casey , Buie Cullen R.
Published: September 2022

Conventional cuvette-based and microfluidics-based electroporation approaches for bacterial gene delivery have distinct advantages, but they are typically limited to relatively small sample volumes, reducing their utility for applications requiring high throughput such as the generation of mutant libraries. Here, we present a scalable, large-scale bacterial gene delivery approach enabled by a disposable, user-friendly microfluidic electroporation device requiring minimal device fabrication and straightforward operation. We demonstrate that the proposed device can outperform conventional cuvettes in a range of situations, including across Escherichia coli strains with a range of electroporation efficiencies, and we use its large-volume bacterial electroporation capability to generate a library of transposon mutants in the anaerobic gut commensal Bifidobacterium longum.
Polygenic signals of sex differences in selection in humans from the UK Biobank
Authors: Ruzicka Filip , Holman Luke , Connallon Tim
Published: September 2022

Sex differences in the fitness effects of genetic variants can influence the rate of adaptation and the maintenance of genetic variation. For example, “sexually antagonistic” (SA) variants, which are beneficial for one sex and harmful for the other, can both constrain adaptation and increase genetic variability for fitness components such as survival, fertility, and disease susceptibility. However, detecting variants with sex-differential fitness effects is difficult, requiring genome sequences and fitness measurements from large numbers of individuals. Here, we develop new theory for studying sex-differential selection across a complete life cycle and test our models with genotypic and reproductive success data from approximately 250,000 UK Biobank individuals. We uncover polygenic signals of sex-differential selection affecting survival, reproductive success, and overall fitness, with signals of sex-differential reproductive selection reflecting a combination of SA polymorphisms and sexually concordant polymorphisms in which the strength of selection differs between the sexes. Moreover, these signals hold up to rigorous controls that minimise the contributions of potential confounders, including sequence mapping errors, population structure, and ascertainment bias. Functional analyses reveal that sex-differentiated sites are enriched in phenotype-altering genomic regions, including coding regions and loci affecting a range of quantitative traits. Population genetic analyses show that sex-differentiated sites exhibit evolutionary histories dominated by genetic drift and/or transient balancing selection, but not long-term balancing selection, which is consistent with theoretical predictions of effectively weak SA balancing selection in historically small populations. Overall, our results are consistent with polygenic sex-differential—including SA—selection in humans. Evidence for sex-differential selection is particularly strong for variants affecting reproductive success, in which the potential contributions of nonrandom sampling to signals of sex differentiation can be excluded.
A sensitive and specific genetically-encoded potassium ion biosensor for in vivo applications across the tree of life
Authors: Wu Sheng-Yi , Wen Yurong , Serre Nelson B. C. , Laursen Cathrine Charlotte Heiede , Dietz Andrea Grostøl , Taylor Brian R. , Drobizhev Mikhail , Molina Rosana S. , Aggarwal Abhi , Rancic Vladimir , Becker Michael , Ballanyi Klaus , Podgorski Kaspar , Hirase Hajime , Nedergaard Maiken , Fendrych Matyáš , Lemieux M. Joanne , Eberl Daniel F. , Kay Alan R. , Campbell Robert E. , Shen Yi
Published: September 2022

Potassium ion (K+) plays a critical role as an essential electrolyte in all biological systems. Genetically-encoded fluorescent K+ biosensors are promising tools to further improve our understanding of K+-dependent processes under normal and pathological conditions. Here, we report the crystal structure of a previously reported genetically-encoded fluorescent K+ biosensor, GINKO1, in the K+-bound state. Using structure-guided optimization and directed evolution, we have engineered an improved K+ biosensor, designated GINKO2, with higher sensitivity and specificity. We have demonstrated the utility of GINKO2 for in vivo detection and imaging of K+ dynamics in multiple model organisms, including bacteria, plants, and mice.
MouseNet: A biologically constrained convolutional neural network model for the mouse visual cortex
Authors: Shi Jianghong , Tripp Bryan , Shea-Brown Eric , Mihalas Stefan , A. Buice Michael
Published: September 2022

Convolutional neural networks trained on object recognition derive inspiration from the neural architecture of the visual system in mammals, and have been used as models of the feedforward computation performed in the primate ventral stream. In contrast to the deep hierarchical organization of primates, the visual system of the mouse has a shallower arrangement. Since mice and primates are both capable of visually guided behavior, this raises questions about the role of architecture in neural computation. In this work, we introduce a novel framework for building a biologically constrained convolutional neural network model of the mouse visual cortex. The architecture and structural parameters of the network are derived from experimental measurements, specifically the 100-micrometer resolution interareal connectome, the estimates of numbers of neurons in each area and cortical layer, and the statistics of connections between cortical layers. This network is constructed to support detailed task-optimized models of mouse visual cortex, with neural populations that can be compared to specific corresponding populations in the mouse brain. Using a well-studied image classification task as our working example, we demonstrate the computational capability of this mouse-sized network. Given its relatively small size, MouseNet achieves roughly 2/3rds the performance level on ImageNet as VGG16. In combination with the large scale Allen Brain Observatory Visual Coding dataset, we use representational similarity analysis to quantify the extent to which MouseNet recapitulates the neural representation in mouse visual cortex. Importantly, we provide evidence that optimizing for task performance does not improve similarity to the corresponding biological system beyond a certain point. We demonstrate that the distributions of some physiological quantities are closer to the observed distributions in the mouse brain after task training. We encourage the use of the MouseNet architecture by making the code freely available.
Deploying wearable sensors for pandemic mitigation: A counterfactual modelling study of Canada’s second COVID-19 wave
Authors: Duarte Nathan , Arora Rahul K. , Bennett Graham , Wang Meng , Snyder Michael P. , Cooperstock Jeremy R. , Wagner Caroline E.
Published: September 2022

Wearable sensors can continuously and passively detect potential respiratory infections before or absent symptoms. However, the population-level impact of deploying these devices during pandemics is unclear. We built a compartmental model of Canada’s second COVID-19 wave and simulated wearable sensor deployment scenarios, systematically varying detection algorithm accuracy, uptake, and adherence. With current detection algorithms and 4% uptake, we observed a 16% reduction in the second wave burden of infection; however, 22% of this reduction was attributed to incorrectly quarantining uninfected device users. Improving detection specificity and offering confirmatory rapid tests each minimized unnecessary quarantines and lab-based tests. With a sufficiently low false positive rate, increasing uptake and adherence became effective strategies for scaling averted infections. We concluded that wearable sensors capable of detecting presymptomatic or asymptomatic infections have potential to help reduce the burden of infection during a pandemic; in the case of COVID-19, technology improvements or supporting measures are required to keep social and resource costs sustainable.
Knowledge, attitude, and practice of Bangladeshi urban slum dwellers towards COVID-19 transmission-prevention: A cross-sectional study
Authors: Hasan Md. Zahid , Hasan A. M. Rumayan , Rabbani Md. Golam , Selim Mohammad Abdus , Mahmood Shehrin Shaila
Published: September 2022

The first COVID-19 case in Bangladesh was detected on March 8, 2020. Since then, efforts are being made across the country to raise awareness among the population for preventing the spread of this virus. We aimed to examine the urban slum dwellers’ knowledge, attitude, and practice (KAP) towards COVID-19 transmission-prevention. A phone-based cross-sectional survey was conducted in five slums of Dhaka City. Total 476 adult slum dwellers were interviewed between October 31 to December 1, 2020 using a pre-tested questionnaire. During an interview, information was collected on participants’ demographic characteristics and KAP items towards COVID-19. We used quartiles for categorization of knowledge and practice score where the first quartile represents poor, the second and third quartiles represent average while the fourth quartile represents good. Attitude score was standardized using z-score and identified as positive and negative attitude. Multiple linear regression models were used separately to identify the socioeconomic predictors of the KAP scores. The results showed that 25% of the respondents had good knowledge and 25% had poor knowledge, 48% had a positive attitude and 52% had a negative attitude, and 21% maintained good practice and 33% maintained poor practice towards COVID-19 transmission-prevention. About 75% respondents relied on television for COVID-19 related information. Regression results showed that knowledge and attitude scores were significantly higher if respondents had primary or secondary and above level of education compared to the uneducated group. Female respondents maintained significantly good practice compared to their male counterparts (β = 6.841; p<0.01). This study has found that one third of the studied slum dwellers maintained poor practice and one fourth had poor knowledge towards COVID-19 transmission-prevention. As KAP domains are significantly correlated, efforts are needed to raise awareness of COVID-19 particularly targeting individuals with average and lower knowledge to improve attitude and practice for the prevention of COVID-19.
Urban rats as carriers of invasive Salmonella Typhimurium sequence type 313, Kisangani, Democratic Republic of Congo
Authors: Falay Dadi , Hardy Liselotte , Tanzito Jacques , Lunguya Octavie , Bonebe Edmonde , Peeters Marjan , Mattheus Wesley , Van Geet Chris , Verheyen Erik , Akaibe Dudu , Katuala Pionus , Ngbonda Dauly , Weill François-Xavier , Pardos de la Gandara Maria , Jacobs Jan
Published: September 2022

Background

Invasive non-typhoidal Salmonella (iNTS–mainly serotypes Enteritidis and Typhimurium) are major causes of bloodstream infections in children in sub-Saharan Africa, but their reservoir remains unknown. We assessed iNTS carriage in rats in an urban setting endemic for iNTS carriage and compared genetic profiles of iNTS from rats with those isolated from humans.

Methodology/Principal findings

From April 2016 to December 2018, rats were trapped in five marketplaces and a slaughterhouse in Kisangani, Democratic Republic of the Congo. After euthanasia, blood, liver, spleen, and rectal content were cultured for Salmonella. Genetic relatedness between iNTS from rats and humans—obtained from blood cultures at Kisangani University Hospital—was assessed with multilocus variable-number tandem repeat (VNTR) analysis (MLVA), multilocus sequence typing (MLST) and core-genome MLST (cgMLST). 1650 live-capture traps yielded 566 (34.3%) rats (95.6% Rattus norvegicus, 4.4% Rattus rattus); 46 (8.1%) of them carried Salmonella, of which 13 had more than one serotype. The most common serotypes were II.42:r:- (n = 18 rats), Kapemba (n = 12), Weltevreden and Typhimurium (n = 10, each), and Dublin (n = 8). Salmonella Typhimurium belonged to MLST ST19 (n = 7 rats) and the invasive ST313 (n = 3, isolated from deep organs but not from rectal content). Sixteen human S. Typhimurium isolates (all ST313) were available for comparison: MLVA and cgMLST revealed two distinct rat-human clusters involving both six human isolates, respectively, i.e. in total 12/16 human ST313 isolates. All ST313 Typhimurium isolates from rats and humans clustered with the ST313 Lineage 2 isolates and most were multidrug resistant; the remaining isolates from rats including S. Typhimurium ST19 were pan-susceptible.

Conclusion

The present study provides evidence of urban rats as potential reservoirs of S. Typhimurium ST313 in an iNTS endemic area in sub-Saharan Africa.
Laboratory evaluation of RealStar Yellow Fever Virus RT-PCR kit 1.0 for potential use in the global yellow fever laboratory network
Authors: Basile Alison J. , Niedrig Matthias , Lambert Amy J. , Meurant Robyn , Brault Aaron C. , Domingo Cristina , Goodman Christin H. , Johnson Barbara W. , Mossel Eric C. , Mulders Mick N. , Velez Jason O. , Hughes Holly R.
Published: September 2022

Background

Early detection of human yellow fever (YF) infection in YF-endemic regions is critical to timely outbreak mitigation. African National Laboratories chiefly rely on serological assays that require confirmation at Regional Reference Laboratories, thus delaying results, which themselves are not always definitive often due to antibody cross-reactivity. A positive molecular test result is confirmatory for YF; therefore, a standardized YF molecular assay would facilitate immediate confirmation at National Laboratories. The WHO-coordinated global Eliminate Yellow Fever Epidemics Laboratory Technical Working Group sought to independently evaluate the quality and performance of commercial YF molecular assays relevant to use in countries with endemic YF, in the absence of stringent premarket assessments. This report details a limited laboratory WHO-coordinated evaluation of the altona Diagnostics RealStar Yellow Fever Virus RT-PCR kit 1.0.

Methodology and principal findings

Specific objectives were to assess the assay’s ability to detect YF virus strains in human serum from YF-endemic regions, determine the potential for interference and cross-reactions, verify the performance claims as stated by the manufacturer, and assess usability. RNA extracted from normal human serum spiked with YF virus showed the assay to be precise with minimal lot-to-lot variation. The 95% limit of detection calculated was approximately 1,245 RNA copies/ml [95% confidence interval 497 to 1,640 copies/ml]. Positive results were obtained with spatially and temporally diverse YF strains. The assay was specific for YF virus, was not subject to endogenous or exogenous interferents, and was clinically sensitive and specific. A review of operational characteristics revealed that a positivity cutoff was not defined in the instructions for use, but otherwise the assay was user-friendly.

Conclusions and significance

The RealStar Yellow Fever Virus RT-PCR kit 1.0 has performance characteristics consistent with the manufacturer’s claims and is suitable for use in YF-endemic regions. Its use is expected to decrease YF outbreak detection times and be instrumental in saving lives.
Methylation levels assessment with Methylation-Sensitive High-Resolution Melting (MS-HRM)
Authors: Samsø Mathiasen Sally , Bińkowski Jan , Kjeldsen Tina , Wojdacz Tomasz K. , Hansen Lise Lotte
Published: September 2022

Testing for disease-related DNA methylation changes provides clinically relevant information in personalized patient care. Methylation-Sensitive High-Resolution Melting (MS-HRM) is a method used for measuring methylation changes and has already been used in diagnostic settings. This method utilizes one set of primers that initiate the amplification of both methylated and non-methylated templates. Therefore, the quantification of the methylation levels using MS-HRM is hampered by the PCR bias phenomenon. Some approaches have been proposed to calculate the methylation level of samples using the high-resolution melting (HRM) curves. However, limitations of the methylation calculation using MS-HRM have not been evaluated systematically and comprehensively. We used the Area Under the Curve (AUC), a derivative of the HRM curves, and least square approximation (LSA) to establish a procedure that allowed us to infer methylation levels in an MS-HRM experiment and assess the limitations of that procedure for the assays’ specific methylation level measurement. The developed procedure allowed, with certain limitations, estimation of the methylation levels using HRM curves.