bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge, attitudes, and practices associated with zoonotic disease transmission risk in North Sulawesi, Indonesia
Authors: Kusumaningrum Tina , Latinne Alice , Martinez Stephanie , Kalengkongan Jusuf , Wiyatno Ageng , Dewantari Aghnianditya Kresno , Kasenda Novie , Bernadus Janno B. B. , Jaya Ungke Anton , Ma’roef Chairin Nisa , Francisco Leilani , Hagan Emily , Miller Maureen , Myint Khin Saw Aye , Daszak Peter , Olival Kevin J. , Saputro Suryo , Pamungkas Joko , Safari Dodi
Published: June 2022

Background

Hunters, vendors, and consumers are key actors in the wildlife trade value chain in North Sulawesi, Indonesia, and potentially face an elevated risk of exposure to zoonotic diseases. Understanding the knowledge, attitudes, and practices (KAP) associated with the risk of zoonotic disease transmission in these communities is therefore critical for developing recommendations to prevent or mitigate zoonotic outbreaks in the future.

Methods

Qualitative and quantitative methods were combined to understand KAP associated zoonotic diseases transmission risk in communities involved in the wildlife trade in North Sulawesi. Qualitative data were collected through semi-structured ethnographic interviews and focus group discussions (FGDs) while quantitative data were collected using questionnaires. We conducted 46 ethnographic interviews and 2 FGDs in 2016, and 477 questionnaire administrations in 2017–2018 in communities from five districts in North Sulawesi. We also collected biological specimens, including nasal swab, oropharyngeal swab, and blood, from 254 participants. The study sites were targeted based on known wildlife consumption and trade activities. The participants for qualitative data collection were purposively selected while participants for quantitative data collection were randomly selected. Biological samples were tested for five viral families including Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae.

Results

Knowledge regarding disease transmission from animals to humans was similar across the participants in qualitative focus groups, including knowledge of rabies and bird flu as zoonotic diseases. However, only a small fraction of the participants from the quantitative group (1%) considered that contact with wild animals could cause sickness. Our biological specimen testing identified a single individual (1/254, 0.004%) who was sampled in 2018 with serological evidence of sarbecovirus exposure. Overall, participants were aware of some level of risk in working with open wounds while slaughtering or butchering an animal (71%) but most did not know what the specific risks were. However, significant differences in the attitudes or beliefs around zoonotic disease risk and health seeking behaviors were observed across our study sites in North Sulawesi.

Conclusions

Our study showed variable levels of knowledge, attitudes, and practices associated with the risk of zoonotic disease transmission among study participants. These findings can be used to develop locally responsive recommendations to mitigate zoonotic disease transmission.
SRR metamaterial-based broadband patch antenna for wireless communications
Authors: Kaur Preet , Bansal Sonia , Kumar Navdeep
Published: June 2022

This paper presents the design and analysis of a broad-band patch antenna using split ring metamaterial. The SRR metamaterial structures are embedded in a unique and novel way in the patch antenna, so that subwavelength modes get introduced in the patch cavity and a broad bandwidth antenna with good performance characteristics is obtained. A rectangular microstrip patch antenna is taken as a reference antenna, which resonates at a frequency of 5.2 GHz and has an impedance bandwidth of 70 MHz. To improve the bandwidth of the patch antenna, firstly the split ring resonator (SRR) is designed according to the reference patch antenna. The optimized SRR metamaterial is placed in between the patch and ground plane of the proposed antenna. The – 10 dB impedance bandwidth of the metamaterial-embedded proposed antenna is 1.63–4.88 GHz and has an average gain of 4.5 dB. The Prototype of the proposed antenna and reference antenna is fabricated and experimental results are obtained. Experimental and simulated results are in good agreement. The presented antenna can be used for LTE, GSM, WiMAX, Bluetooth, and other wireless applications.
The truncated form of flagellin (tFlic) provides the 2dCap subunit vaccine with better immunogenicity and protective effects in mice
Authors: Lu Ying , Liu Zehui , Li Yingxiang , Deng Zhuofan , Fang Weihuan , He Fang
Published: June 2022

Porcine circovirus type 2 (PCV2) is the main causative agent of porcine circovirus-associated diseases, and it causes substantial economic losses in the swine industry each year. It is crucial to develop an effective vaccine against the circulating strain PCV2d, which is prone to substantial degrees of mutation. In this study, a truncated form of flagellin (tFlic: 85-111 aa) was inserted into the C-terminal sequence of 2dCap, and Western blotting results showed that recombinant Cap-tFlic VLPs were successfully expressed. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) data indicated that purified recombinant Cap-tFlic fusion proteins existed in the form of polymers and that tFlic could not affect the formation and internalization of VLPs. Integrated Cap-tFlic VLPs induced the expression of antigen presentation-related factors (MHC-II and CD86) by bone marrow-derived dendritic cells (BM-DCs), and the expression of TLR5-related factors (TNF-α) was dramatically elevated. Mice intramuscularly immunized with Cap-tFlic VLPs exhibited significantly higher levels of Cap-specific antibodies and neutralizing antibodies than mice immunized with wild-type Cap VLPs. The data obtained in the current study indicate that Cap-tFlic may be a candidate for a subunit vaccine against PCV2 in the future.
In the Shadow of the Palms
Authors: Chao Sophie
Published: June 2022

Sophie Chao examines the multispecies entanglements of oil palm plantations in West Papua, Indonesia, showing how Indigenous Marind communities understand and navigate the social, political, and environmental demands of the oil palm plant.
Efficient Strategy for the Preparation of Chemical Probes of Biologically Active Glycosides Using a Boron-Mediated Aglycon Delivery (BMAD) Method
Authors: Kimura Kosuke , Yasunaga Takeshi , Makikawa Takumi , Takahashi Daisuke , Toshima Kazunobu
Published: June 2022

Development of an efficient method for the analysis and identification of the target proteins with which biologically active glycosides directly interact is highly desirable in many research fields. In this article, we report an efficient strategy for the preparation of chemical probes of biologically active glycosides using a reaction sequence of i) a boron-mediated aglycon delivery (BMAD) with an N3-functionalized 1,2-anhydroglucose donor, ii) deprotection, and iii) strain-promoted azide-alkyne cycloaddition. Using the synthesized chemical probes, we successfully demonstrated that the target proteins of a cardiac glycoside, lanatoside C (1), can be visualized and identified in human colon cancer HCT116 cells.
Sex-Specific Physiological Responses to Ultramarathon
Authors: TILLER NICHOLAS B. , WHEATLEY-GUY COURTNEY M. , FERMOYLE CAITLIN C. , ROBACH PAUL , ZIEGLER BRIANA , GAVET ALICE , SCHWARTZ JESSE C. , TAYLOR BRYAN J. , CONSTANTINI KEREN , MURDOCK ROBERT , JOHNSON BRUCE D. , STEWART GLENN M.
Published: June 2022

Purpose

Despite a growing body of literature on the physiological responses to ultramarathon, there is a paucity of data in females. This study assessed the female physiological response to ultramarathon and compared the frequency of perturbations to a group of race- and time-matched males.

Methods

Data were collected from 53 contestants of an ultramarathon trail race at the Ultra-Trail du Mont-Blanc (UTMB®) in 2018/19. Before and within 2 h of the finish, participants underwent physiological assessments, including blood sampling for biomarkers (creatine kinase–MB isoenzyme [CK-MB], cardiac troponin I [cTnI], brain natriuretic peptide [BNP], and creatinine [Cr]), pulmonary function testing (spirometry, exhaled NO, diffusing capacities, and mouth pressures), and transthoracic ultrasound (lung comet tails, cardiac function). Data from eight female finishers (age = 36.6 ± 6.9 yr; finish time = 30:57 ± 11:36 h:min) were compared with a group of eight time-matched males (age = 40.3 ± 8.3 yr; finish time = 30:46 ± 10:32 h:min).

Results

Females exhibited significant pre- to postrace increases in BNP (25.8 ± 14.6 vs 140.9 ± 102.7 pg·mL−1; P = 0.007) and CK-MB (3.3 ± 2.4 vs 74.6 ± 49.6 IU·L−1; P = 0.005), whereas males exhibited significant pre- to postrace increases in BNP (26.6 ± 17.5 vs 96.4 ± 51.9 pg·mL−1; P = 0.002), CK-MB (7.2 ± 3.9 vs 108.8 ± 37.4 IU·L−1; P = 0.002), and Cr (1.06 ± 0.19 vs 1.23 ± 0.24 mg·dL−1; P = 0.028). Lung function declined in both groups, but males exhibited additional reductions in lung diffusing capacities (DLCO = 34.4 ± 5.7 vs 29.2 ± 6.9 mL⋅min−1⋅mm Hg−1, P = 0.004; DLNO = 179.1 ± 26.2 vs 152.8 ± 33.4 mL⋅min−1⋅mm Hg−1, P = 0.002) and pulmonary capillary blood volumes (77.4 ± 16.7 vs 57.3 ± 16.1 mL; P = 0.002). Males, but not females, exhibited evidence of mild postrace pulmonary edema. Pooled effect sizes for within-group pre- to postrace changes, for all variables, were generally larger in males versus females (d = 0.86 vs 0.63).

Conclusions

Ultramarathon negatively affects a range of physiological functions but generally evokes more frequent perturbations, with larger effect sizes, in males compared to females with similar race performances.
Racial Isolation and Marginalization of Economic Research on Race and Crime
Authors: Mason Patrick L. , Myers Samuel L. , Simms Margaret
Published: June 2022

This essay examines the extent to which research on the economics of race and crime produced by Black economists or published in the flagship journal of the organization of Black economists, the Review of Black Political Economy (RBPE), is undervalued by mainstream economics. We use modern bibliometric methods to test for citation biases in the economics of crime literature. We also identify the contributions of three streams of research overlooked in the mainstream literature: identity, police use of force, and mass incarceration. We find evidence that Blacks publishing on race and crime in top economics journals are less likely to be cited than non-Blacks and that articles published in the RBPE are less likely to be cited than articles published in other journals. A review of some under-cited articles reveals that themes related to identity, police use of force, and mass incarceration hold valuable insights for policy makers and those seeking solutions to problems of persistent racial disparities in the criminal legal system. (JEL A11, A14, H75, J15, K42)
La lógica difusa como herramienta para la toma de decisiones en empresas venezolanas de servicios privados de salud médica
Authors: Briceño Núñez Chess Emmanuel , Durán Sánchez Yosmary Carolina , Montilla Soto Alen David
Published: June 2022

En este artículo presenta la aplicación de herramientas para la toma de decisiones, con la finalidad Simples. Para ello se empleó la lógica difusa o matemática borrosa con sus respectivos procedimientos y criterios de elección. Se realizaron los cálculos con cada uno de los siguientes instrumentos: Distancia de Hamming, Coeficiente de adecuación (sin y con ponderación convexa), Índice de máximo y mínimo nivel con ponderación convexa, y la teoría de los efectos olvidados; así como el Umbral de Rentabilidad, utilizando para ello, el programa Excel. Fueron considerados buenos por los expertos, los programas: Imagen, Reputación, Trato y Relación, porque mientras más relación y trato haya de los directos con los empleados, más compenetración en el trabajo habrá, se aportarán nuevas ideas para la solución de problemas y los empleados se sentirán identificados con la empresa por tomarlos en cuenta. Por otra parte, mientras mayor reputación e imagen tenga, la empresa mejorará su servicio de calidad, no solo en el área de hospitalización en piso, sino en todos los servicios que ofrece.
Impressionable or Immune? Examining the Influence of Marquee Sellers in B2B Secondary Market Platforms for IT Products
Authors: Alhauli Abdullah , Elmaghraby Wedad J. , Gopal Anandasivam
Published: June 2022

Consumers around the world have moved dramatically toward online platforms. Purchasing goods and services from independent suppliers through digital platforms has become a routine part of daily life. Recently, the COVID-19 pandemic has accelerated the paradigm shift toward digital economy and servitization. Data show that ecommerce sales have grown by $32 billion during the last two years ( https://www.digitalcommerce360.com/article/coronavirus-impact-online-retail/ ). A large part of this ecommerce is on platforms-based models, where management of the platform community remains a difficult problem. One such question often discussed in the platforms context remains: Does acquiring a marquee seller help the platform owner? If so, how exactly? We show that in the specific context of B2B platforms, the impact of a marquee seller’s presence is significantly positive on prices obtained by other sellers on the platform. This is because the marquee seller generates higher prices, given its brand, and these prices become reference prices for other sellers. The managerial implications highlight the importance of acquiring marquee sellers and encourage platform owners to understand the associated price effects. Our paper suggests that platform owners should consider and target sellers with marquee brand names, as they can result in a sugar-rush for prices of other sellers on the platform.
Learning Motivation, Democratic Parenting, and Peer Relations Predict Academic Self-Concept
Authors: Ningsih Risaniatin , Degeng I Nyoman Sudana , Triyono Triyono , Ramli M.
Published: June 2022

Students' academic self-concept is a concerning concept in educational research. The purpose of this research is to examine the simultaneous influence and relationship of learning motivation, democratic parenting, and peer relations with academic self-concept in students. This is a correlational research with a cluster random sampling method used to collect data from 962 students. The result showed that learning motivation, democratic parenting, and peer relations had a partial and simultaneous relationship with students' academic self-concept. Furthermore, support from guidance and counselors, homeroom teachers, and parents is essential for students to actualize and develop their character optimally and effectively.  
Assessment of Optimum Mechanical Properties for Friction Stir Welding of Pure Copper and Aluminium Bronze
Authors:   Department of Production Engineering, Government College of Technology, Coimbatore, Tamilnadu 641013, India, Nagalingam Ajaymanikandan , Palanivel Ilamathi ,   Department of Production Engineering, Government College of Technology, Coimbatore, Tamilnadu 641013, India, Ramanathan Thirumalai ,   Department of Mechanical Engineering, Dr.N.G.P Institute of Technology, Coimbatore, Tamilnadu 641048, India
Published: June 2022

Joining Aluminium Bronze and copper alloys has more comprehensive applications like power distribution, marine and automotive sectors and conventional fusion welding techniques impairs the weld quality owing to the high temperatures required. Friction stir welding is a preferred technique for fusing these alloys. This process eliminates many common problems associated with fusion welding like oxidization of aluminium, porosity, hot cracking. In recent years, there has been a lot of research into employing friction stir welding to fuse incompatible metals and alloys. Mechanical parameters such as hardness, yield strength elongation and ultimate tensile strength in friction stir welded joints of pure copper and aluminium bronze are investigated in this study. Each of the parameters, such as axial force, tool rotational speed and traverse speed was varied three levels each. A mathematical model based on a face-centered central composite design was used to study the effect of welding parameters on output responses. The selected friction stir welding parameters have a considerable impact on the output responses that are measured. The optimum process parameters for increasing the mechanical characteristics of welded joints were determined to be 1000 rpm tool rotation speed, 30 mm/min traverse speed, and 4.5 kN axial force.
Prosumption for Social Sustainability: Social-media Posting of DIY-cooking Outcomes During COVID-19
Authors: Trivedi Vibha , Pandey Krishan Kumar , Trivedi Ashish
Published: June 2022

Sharing of Do-It-Yourself (DIY) cooking outcomes on various social media platforms was one of the most visible phenomena on the digital landscapes during COVID-19 led lockdowns. Since the prosumption of food is not considered as a source of alternative food system only, but also as a source of pleasure, DIY-cooking-related social media posts during the lockdown were prevalent among internet users. This paper examines variations in the social media posting behavior of food prosumers based on four individual and three social factors of gender, age, marital status, and family structure. Responses from 198 Facebook food community members were used to test the statistical hypotheses. The analyses report that the need for entertainment value while posting on social media was different among different demographic factors, whereas self-discovery and social enhancement did not exhibit variations across demographics. The need for social presence mattered more for unmarried people during social isolation whereas females used DIY-cooking posting to fulfil the need for uniqueness. The implications for social sustainability and business practices are also discussed.
June 2022 Medical Image of the Month: A Hard Image to Swallow
Authors:   Department of Critical Care Medicine, Franciscan Health, Olympia Fields, Illinois USA, Carrillo Alessandra , , Ondracek Robert , Punatar Shil , Ondracek Andrew , Sundaram Ravi
Published: June 2022

No abstract available. Article truncated after 150 words. Introduction: Esophageal food impactions are common occurrences in gastroenterology, however, under 20% of cases require intervention (1) .The clinical condition of the esophagus and the consistency of food being swallowed contribute to the development of food bolus impactions, with patients having underlying esophageal pathology in most cases (2). Unfortunately, radiographic evidence is often difficult to obtain as food is radiolucent and poorly visualized on radiograph. Here, we demonstrate the risk associated with severe food impaction. Case Presentation: An 86-year-old man with a past medical history of achalasia with laparoscopic Heller myotomy complicated by distal esophageal perforation, was admitted after presenting with complaints of chest pain and inability to tolerate a solid diet. Additionally, he suffered a 90-pound weight loss over 1 year. He was seen by speech therapy and provided with a dysphagia appropriate diet. Eight days into the patient stay, the family presented to the patient's bedside to assist …
Amplification of high-intensity pressure waves and cavitation in water using a multi-pulsed laser excitation and black-TiOx optoacoustic lens
Authors: Tašič Muc Blaž , Vella Daniele , Lukač Nejc , Kos Matjaž , Jezeršek Matija
Published: June 2022

A method for amplification of high-intensity pressure waves generated with a multi-pulsed Nd:YAG laser coupled with a black-TiOx optoacoustic lens in the water is presented and characterized. The investigation was focused on determining how the multi-pulsed laser excitation with delays between 50 µs and 400 µs influences the dynamics of the bubbles formed by a laser-induced breakdown on the upper surface of the lens, the acoustic cavitation in the focal region of the lens, and the high-intensity pressure waves generation. A needle hydrophone and a high-speed camera were used to analyze the spatial distribution and time-dependent development of the above-mentioned phenomena. Our results show how different delays (td) of the laser pulses influence optoacoustic dynamics. When td is equal to or greater than the bubble oscillation time, acoustic cavitation cloud size increases 10-fold after the fourth laser pulse, while the pressure amplitude increases by more than 75%. A quasi-deterministic creation of cavitation due to consecutive transient pressure waves is also discussed. This is relevant for localized ablative laser therapy.
Modulation bandwidth improvement of III-V/Si hybrid MOS optical modulator by reducing parasitic capacitance
Authors: Tang Hanzhi , Li Qiang , Ho Chong Pei , Fujikata Junichi , Noguchi Masataka , Takahashi Shigeki , Toprasertpong Kasidit , Takagi Shinichi , Takenaka Mitsuru
Published: June 2022

In this work, we numerically and experimentally examined the impact of parasitic capacitance on the modulation bandwidth of a III-V/Si hybrid metal-oxide-semiconductor (MOS) optical modulator. The numerical analysis revealed that the parasitic capacitance between the III-V membrane and the Si slab should be considered to achieve high-speed modulation, particularly in the case of a thick gate oxide. We also fabricated a high-speed InGaAsP/Si hybrid MOS optical modulator with a low capacitance using a SiO2-embedded Si waveguide. The fabricated device exhibited a modulation efficiency of 0.245 Vcm and a 3 dB bandwidth of up to 10 GHz. Clear eye patterns with 25 Gbps non-return-to-zero (NRZ) modulation and 40 Gbps 4-level pulse amplitude modulation (PAM-4) were obtained without pre-emphasis.
Mode-selective modulator and switch based on graphene-polymer hybrid waveguides
Authors: Lian Tianhang , Zhu Mu , Sun Shijie , Sun Xueqing , Che Yuanhua , Lin Baizhu , Wang Xibin , Zhang Daming
Published: June 2022

The mode-division multiplexing (MDM) is an effective technology with huge development potential to improve the transmission capacity of optical communication system by transmitting multiple modes simultaneously in a few-mode fiber. In traditional MDM technology, the fundamental modes of multiple channels are usually modulated by external individual arranged electro-optic modulators, and then multiplexed into the few-mode fiber or waveguide by a mode multiplexer. However, this is usually limited by large device footprint and high power consumption. Here, we report a mode-selective modulator and switch to individually modulate or switch the TE11, TE12 and TE21 modes in a few-mode waveguide (FMW) to overcome this limitation. Our method is based on the graphene-polymer hybrid platform with four graphene capacitors buried in different locations of the polymer FMW by utilizing the coplanar interaction between the capacitors and spatial modes. The TE11, TE12 and TE21 modes in the FMW can be modulated and switched separately or simultaneously by applying independent gate voltage to different graphene capacitor of the device. Our study is expected to make the selective management of the spatial modes in MDM transmission systems more flexible.
Quantum correlation propagation in a waveguide-QED system with long-range interaction
Authors: Xing Fan , Lu Yunning , Liao Zeyang
Published: June 2022

We investigate the excitation and correlation propagations among a one-dimensional atom chain with exponentially decaying, ideal long-range, and power-law decaying interactions. We show that although a clear light-cone-like structure can appear in both the excitation and correlation propagation patterns under the exponentially decaying interaction, only an obscure light-cone-like structure appears with multi-power-law decaying interaction and surprisingly an inverse light-cone-like structure appears in the ideal long-range interaction case. The extracted excitation and correlation propagation velocities in the ideal long-range interaction case are about one order of magnitude larger than those in the multi-power-law interaction case and about two orders of magnitude larger than those in the short-range interaction case. These results indicate that the waveguide-quantum electrodynamics system with long-range interaction can boost the quantum information transfer speed and is beneficial for building fast quantum network and scalable quantum computer.
Active linearized PGC demodulation with fusion of PGC-Arctan and PGC-DCM schemes for nonlinear error elimination in SPM interferometer
Authors: Chen Benyong , Jiang Jiancheng , Lou Yingtian , Yan Liping
Published: June 2022

To eliminate the nonlinear error of phase generated carrier (PGC) demodulation in sinusoidal phase modulating interferometer (SPMI), an active linearized PGC demodulation with fusion of differential-and-cross-multiplying (PGC-DCM) and the arctangent (PGC-Arctan) schemes is proposed. In this method, the periodic integer multiple of π (π-integer phases) of PGC-Arctan without nonlinear error and the corresponding PGC-DCM results recorded at the same time are fused to obtain a calibration coefficient for PGC-DCM demodulation. Combining the accurate π-integer phases of PGC-Arctan and the calibrated fractional phase in the range of π of PGC-DCM, a linearized PGC demodulation result can be achieved, effectively eliminating the nonlinear error caused by drifts of phase demodulation depth (m) and carrier phase delay (θ). The distinct advantage of the proposed method is that it actively and linearly calibrates the fractional result of PGC-DCM without needing to measure or compensate m and θ. Simulation and displacement measurement experiments with different m and inherent arbitrary θ are performed to validate the proposed method. The experimental results show that nonlinear error of the proposed method can be reduced to about 0.1 nm with real-time linearization.
Subcellular mechano-microscopy: high resolution three-dimensional elasticity mapping using optical coherence microscopy
Authors: Mowla Alireza , Li Jiayue , Hepburn Matt S. , Maher Samuel , Chin Lixin , Yeoh George C. , Choi Yu Suk , Kennedy Brendan F.
Published: June 2022

The importance of cellular-scale mechanical properties is
well-established, yet it is challenging to map subcellular elasticity
in three dimensions. We present subcellular mechano-microscopy, an
optical coherence microscopy (OCM)-based variant of three-dimensional
(3-D) compression optical coherence elastography (OCE) that provides
an elasticity system resolution of 5 × 5 × 5 µm: a 7-fold improvement
in system resolution over previous OCE studies of cells. The improved
resolution is achieved through a ∼5-fold improvement in optical
resolution, refinement of the strain estimation algorithm, and
demonstration that mechanical deformation of subcellular features
provides feature resolution far greater than that demonstrated
previously on larger features with diameter >250 µm. We use
mechano-microscopy to image adipose-derived stem cells encapsulated in
gelatin methacryloyl. We compare our results with compression OCE and
demonstrate that mechano-microscopy can provide contrast from
subcellular features not visible using OCE.
Using genetic variation to disentangle the complex relationship between food intake and health outcomes
Authors: Pirastu Nicola , McDonnell Ciara , Grzeszkowiak Eryk J. , Mounier Ninon , Imamura Fumiaki , Merino Jordi , Day Felix R. , Zheng Jie , Taba Nele , Concas Maria Pina , Repetto Linda , Kentistou Katherine A. , Robino Antonietta , Esko Tõnu , Joshi Peter K. , Fischer Krista , Ong Ken K. , Gaunt Tom R. , Kutalik Zoltán , Perry John R. B. , Wilson James F.
Published: June 2022

Diet is considered as one of the most important modifiable factors influencing human health, but efforts to identify foods or dietary patterns associated with health outcomes often suffer from biases, confounding, and reverse causation. Applying Mendelian randomization in this context may provide evidence to strengthen causality in nutrition research. To this end, we first identified 283 genetic markers associated with dietary intake in 445,779 UK Biobank participants. We then converted these associations into direct genetic effects on food exposures by adjusting them for effects mediated via other traits. The SNPs which did not show evidence of mediation were then used for MR, assessing the association between genetically predicted food choices and other risk factors, health outcomes. We show that using all associated SNPs without omitting those which show evidence of mediation, leads to biases in downstream analyses (genetic correlations, causal inference), similar to those present in observational studies. However, MR analyses using SNPs which have only a direct effect on the exposure on food exposures provided unequivocal evidence of causal associations between specific eating patterns and obesity, blood lipid status, and several other risk factors and health outcomes.
A multi-population phenome-wide association study of genetically-predicted height in the Million Veteran Program
Authors: Raghavan Sridharan , Huang Jie , Tcheandjieu Catherine , Huffman Jennifer E. , Litkowski Elizabeth , Liu Chang , Ho Yuk-Lam A. , Hunter-Zinck Haley , Zhao Hongyu , Marouli Eirini , North Kari E. ,   the VA Million Veteran Program, Lange Ethan , Lange Leslie A. , Voight Benjamin F. , Gaziano J. Michael , Pyarajan Saiju , Hauser Elizabeth R. , Tsao Philip S. , Wilson Peter W. F. , Chang Kyong-Mi , Cho Kelly , O’Donnell Christopher J. , Sun Yan V. , Assimes Themistocles L.
Published: June 2022

Background

Height has been associated with many clinical traits but whether such associations are causal versus secondary to confounding remains unclear in many cases. To systematically examine this question, we performed a Mendelian Randomization-Phenome-wide association study (MR-PheWAS) using clinical and genetic data from a national healthcare system biobank.

Methods and findings

Analyses were performed using data from the US Veterans Affairs (VA) Million Veteran Program in non-Hispanic White (EA, n = 222,300) and non-Hispanic Black (AA, n = 58,151) adults in the US. We estimated height genetic risk based on 3290 height-associated variants from a recent European-ancestry genome-wide meta-analysis. We compared associations of measured and genetically-predicted height with phenome-wide traits derived from the VA electronic health record, adjusting for age, sex, and genetic principal components. We found 345 clinical traits associated with measured height in EA and an additional 17 in AA. Of these, 127 were associated with genetically-predicted height at phenome-wide significance in EA and 2 in AA. These associations were largely independent from body mass index. We confirmed several previously described MR associations between height and cardiovascular disease traits such as hypertension, hyperlipidemia, coronary heart disease (CHD), and atrial fibrillation, and further uncovered MR associations with venous circulatory disorders and peripheral neuropathy in the presence and absence of diabetes. As a number of traits associated with genetically-predicted height frequently co-occur with CHD, we evaluated effect modification by CHD status of genetically-predicted height associations with risk factors for and complications of CHD. We found modification of effects of MR associations by CHD status for atrial fibrillation/flutter but not for hypertension, hyperlipidemia, or venous circulatory disorders.

Conclusions

We conclude that height may be an unrecognized but biologically plausible risk factor for several common conditions in adults. However, more studies are needed to reliably exclude horizontal pleiotropy as a driving force behind at least some of the MR associations observed in this study.
An in vivo drug repurposing screen and transcriptional analyses reveals the serotonin pathway and GSK3 as major therapeutic targets for NGLY1 deficiency
Authors: Hope Kevin A. , Berman Alexys R. , Peterson Randall T. , Chow Clement Y.
Published: June 2022

NGLY1 deficiency, a rare disease with no effective treatment, is caused by autosomal recessive, loss-of-function mutations in the N-glycanase 1 (NGLY1) gene and is characterized by global developmental delay, hypotonia, alacrima, and seizures. We used a Drosophila model of NGLY1 deficiency to conduct an in vivo, unbiased, small molecule, repurposing screen of FDA-approved drugs to identify therapeutic compounds. Seventeen molecules partially rescued lethality in a patient-specific NGLY1 deficiency model, including multiple serotonin and dopamine modulators. Exclusive dNGLY1 expression in serotonin and dopamine neurons, in an otherwise dNGLY1 deficient fly, was sufficient to partially rescue lethality. Further, genetic modifier and transcriptomic data supports the importance of serotonin signaling in NGLY1 deficiency. Connectivity Map analysis identified glycogen synthase kinase 3 (GSK3) inhibition as a potential therapeutic mechanism for NGLY1 deficiency, which we experimentally validated with TWS119, lithium, and GSK3 knockdown. Strikingly, GSK3 inhibitors and a serotonin modulator rescued size defects in dNGLY1 deficient larvae upon proteasome inhibition, suggesting that these compounds act through NRF1, a transcription factor that is regulated by NGLY1 and regulates proteasome expression. This study reveals the importance of the serotonin pathway in NGLY1 deficiency, and serotonin modulators or GSK3 inhibitors may be effective therapeutics for this rare disease.
Porcine model of neurocysticercosis by intracarotid injection of Taenia solium oncospheres: Dose assessment, infection outcomes and serological responses
Authors: Arroyo Gianfranco , Toribio Luz , Vargas-Calla Ana , Calcina Juan F. , Bernal Edson , Chile Nancy , Zambrano Miguel , Gomez-Puerta Luis A. , Chacaltana Juan , Marzal Miguel , Bustos Javier A. , Verastegui Manuela R. , Gilman Robert H. , O’Neal Seth E. , Gonzalez Armando E. , Garcia Hector H. ,   for The Cysticercosis Working Group in Peru
Published: June 2022

Background

Neurocysticercosis (NCC) is the infection of the human central nervous system (CNS) byTaenia soliumlarvae that cause significant neurological morbidity. Studies on NCC pathophysiology, host-parasite interactions or therapeutic agents are limited by the lack of suitable animal models. We have previously reported that carotid injection of activatedT.soliumoncospheres directs parasites into the CNS and consistently reproduces NCC. This study assessed the minimal dose required to consistently obtain NCC by intracarotid oncosphere injection and compared antigen and antibody response profiles by dose-group.

Methods/Principal findings

Three groups of pigs were infected with either 2500 (n = 10), 5000 (n = 11), or 10000 (n = 10) oncospheres. Two pigs died during the study. Necropsy exam at day 150 post-infection (PI) demonstrated viable NCC in 21/29 pigs (72.4%), with higher NCC rates with increasing oncosphere doses (4/9 [44.4%], 9/11 [81.8%] and 8/9 [88.9%] for 2500, 5000, and 10000 oncospheres respectively,Pfor trend = 0.035). CNS cyst burden was also higher in pigs with increasing doses (Pfor trend = 0.008). Viable and degenerated muscle cysticerci were also found in all pigs, with degenerated cysticerci more frequent in the 2500 oncosphere dose-group. All pigs were positive for circulating parasite antigens on ELISA (Ag-ELISA) from day 14 PI; circulating antigens markedly increased at day 30 PI and remained high with plateau levels in pigs infected with either 5000 or 10000 oncospheres, but not in pigs infected with 2500 oncospheres. Specific antibodies appeared at day 30 PI and were not different between dose-groups.

Conclusion/Significance

Intracarotid injection of 5000 or more oncospheres produces high NCC rates in pigs with CNS cyst burdens like those usually found in human NCC, making this model appropriate for studies on the pathogenesis of NCC and the effects of antiparasitic treatment.
Social connections at work and mental health during the first wave of the COVID-19 pandemic: Evidence from employees in Germany
Authors: Breetzke Jonas , Wild Eva-Maria
Published: June 2022

Empirical evidence on the social and psychological impact of the COVID-19 pandemic in the workplace and the resulting consequences for the mental health of employees is lacking. As a result, research on this subject is urgently needed to develop appropriate countermeasures. This study builds on Person-Environment fit theory to investigate social connections at work and mental health during the first wave of the COVID-19 pandemic. It analyses employees’ needs for social connections and how social connections affect different mental health measures. Data were collected in May 2020 in an online survey of employees across Germany and analysed using response surface analysis. Mental health was measured as positive mental health and mental health disorders. Social connections were measured as social support and social interactions. 507 employees participated in the survey and more than one third reported having less social support and social interaction at work than they desired (p < .001). This was associated with a decrease in mental health. In contrast, having more than the desired amount of social support was associated with a decrease, and having more than the desired amount of social interaction with an increase, in mental health. This study provides important early evidence on the impact of the first wave of the COVID-19 pandemic in the workplace. With it, we aim to stimulate further research in the field and provide early evidence on the potential mental health consequences of social distancing–while also opening avenues to combat them.
Utilization and cost of drugs for diabetes and its comorbidities and complications in Kuwait
Authors: Alowayesh Maryam S. , Aljunid Syed M. , Al-Adsani Afaf , Alessa Thamer , Alattar Abdulnabi , Alroudhan Dherar
Published: June 2022

Background

Diabetes imposes a large burden on countries’ healthcare expenditures. In Kuwait, diabetes prevalence in adults is estimated at 22.0%%—double the worldwide prevalence (9.3%). There is little current data on pharmaceutical costs in Kuwait of managing diabetes and diabetes-related complications and comorbidities.

Objectives

Estimate the utilization and cost of drugs for diabetes and diabetes-related complications and comorbidities in Kuwait for year 2018, as well determinants of costs.

Methods

This cross-sectional study used a multi-stage stratified sampling method. Patients were Kuwaiti citizens with diabetes, aged 18–80, recruited from all six governorates. Physicians collected demographic data, clinical data, and current drug prescription for each patient which was extrapolated for the full year of 2018. A prevalence-based approach and bottom-up costing were used. Data were described according to facility type (primary care vs. hospital). A generalized linear model with log function and normal distribution compared drug costs for patients with and without comorbidities/complications after adjustments for demographic and health confounders (gender, age group, disease duration, and obesity).

Results

Of 1182 diabetes patients, 64.0% had dyslipidemia and 57.7% had hypertension. Additionally, 40.7% had diabetes-related complications, most commonly neuropathy (19.7%). Of all diabetes patients, 85.9% used oral antidiabetics (alone or in combinations), 49.5% used insulin alone or in combinations, and 29.3% used both oral antidiabetics and insulin. The most frequently used oral drug was metformin (75.7%), followed by DPP4 inhibitors (40.2%) and SGLT2 inhibitors (23.8%). The most frequently used injectables were insulin glargine (36.6%), followed by GLP-1 receptor agonists (15.4%). Total annual drug cost for Kuwait’s diabetic population for year 2018 was US$201 million (US$1,236.30 per patient for antidiabetics plus drugs for comorbidities/complications).

Conclusions

Drug costs for treating diabetes and comorbidities/complications accounted for an estimated 22.8% of Kuwait’s 2018 drug expenditures. Comorbidities and complications add 44.7% to the average drug cost per diabetes patient.
Influence of precedent drug on the subsequent therapy in the sequence of trifluridine/tipiracil with/out bevacizumab and regorafenib for unresectable or recurrent colorectal cancer
Authors: Oshima Kotoe , Hirano Hidekazu , Shoji Hirokazu , Iwasa Satoru , Okita Natsuko , Takashima Atsuo , Boku Narikazu
Published: June 2022

Background

Trifluridine/tipiracil (TFTD), with or without bevacizumab (Bev), and regorafenib are salvage chemotherapy options for metastatic colorectal cancer (mCRC). Here, we examined the influence of precedent drug on the efficacy of subsequent drug.

Method

The subjects were patients with mCRC who received salvage chemotherapy with TFTD (with/without Bev) followed by regorafenib (TFTD→Rego group/TFTD+Bev→Rego group), or reverse sequence (Rego→TFTD group) at the National Cancer Center Hospital between November 2013 and December 2020. The overall survival (OS), progression-free survival (PFS), disease control rate (DCR), tumor growth rate (TGR), and tumor growth kinetics (TGK) in the first evaluation were assessed in the three groups.

Results

A total of 69 patients, including 27 in the TFTD→Rego group, 13 in the TFTD+Bev→Rego group, and 29 in the Rego→TFTD group, were identified. There were no significant differences in the OS among the three groups, and in the PFS and DCR between the precedent and subsequent therapies in any of the groups. The median TGR (%/month) and TGK (mm/month) in the precedent→subsequent therapy were 50.9→32.7 (p = 0.044) and 8.76→7.79 in the TFTD→Rego group, 25.4→36.1 and 7.49→9.92 in the TFTD+Bev→Rego group, and 40.8→24.4 (p = 0.027) and 8.02→7.20 in the Rego→TFTD group, respectively.

Conclusion

In crossover use of TFTD with/without Bev and regorafenib, both agents showed similar efficacy in terms of the conventional parameters, but the differences observed in the TGR and TGK might suggest some influence of prior regorafenib treatment on the efficacy of subsequent TFTD therapy, and vice versa.
Host species and environment drivers of ectoparasite community of rodents in a Mojave Desert wetlands
Authors: López-Pérez Andrés M. , Pesapane Risa , Clifford Deana L. , Backus Laura , Foley Patrick , Voll Ashley , Silva Ricardo Bassini , Foley Janet
Published: June 2022

Drivers of patterns of ectoparasitism in rodents in patchy Mojave Desert wetlands were investigated. A total of 1,571 ectoparasites in Mesostigmata, Trombidiformes, Siphonaptera and Ixodida were collected from 341 rodents (Microtus californicus scirpensis,Mus musculus,Reithrodontomys megalotis,Peromyscus eremicus, andNeotoma lepida) at eleven marshes. Trombiculids accounted for 82.5% of mites, followed by the mesostigmatidOrnithonyssus bacoti(17.5%), with chiggers predominating on voles and harvest mice. There were at least three genera of chiggers (Eutrombicula alfreddugesi,Euschoengastiasp. novel, andBlankaartiasp. novel). Fleas includedOrchopeas leucopus(90.3% of all fleas) andO.sexdentatus(9.7%), and ticks were the novel endemicIxodes mojavensis(82.1% of ticks) andDermacentor similis(17.9%). On all hosts and at all marshes, coverage-based rarefaction sampling was over 96%, indicating coverage sufficient for analysis. Dissimilarities in ectoparasite community structure were driven mainly by chiggers,I.mojavensisandO.leucopus. Northern marshes were dominated by chiggers; central marshes byI.mojavensis; and southern marshes byO.leucopus. Primary determinants of ectoparasite community structure were host species, patch size, and parasite interspecific interactions. Host species richness and environmental factors such as patch distance and water and plant availability were not significantly associated with patterns of ectoparasitism. There were nine (60%) significant negative pairwise associations between ectoparasite taxa and no significant positive relationships.Ixodes mojavensishad the highest number of negative associations (with five other species), followed by chiggers andO.bacotiwith two negative associations each. The study area is among the most arid in North America and supports numerous rare and endemic species in increasingly isolated wetland habitat patches; knowledge of ectoparasite ecology in this region identifies potential ectoparasite vectors, and provides information needed to design and implement programs to manage vector-borne diseases for purposes of wildlife conservation.
Cost-utility analysis of adding abiraterone acetate plus prednisone/prednisolone to long-term hormone therapy in newly diagnosed advanced prostate cancer in England: Lifetime decision model based on STAMPEDE trial data
Authors: Clarke Caroline S. , Hunter Rachael M. , Gabrio Andrea , Brawley Christopher D. , Ingleby Fiona C. , Dearnaley David P. , Matheson David , Attard Gerhardt , Rush Hannah L. , Jones Rob J. , Cross William , Parker Chris , Russell J. Martin , Millman Robin , Gillessen Silke , Malik Zafar , Lester Jason F. , Wylie James , Clarke Noel W. , Parmar Mahesh K. B. , Sydes Matthew R. , James Nicholas D.
Published: June 2022

Adding abiraterone acetate (AA) plus prednisolone (P) to standard of care (SOC) improves survival in newly diagnosed advanced prostate cancer (PC) patients starting hormone therapy. Our objective was to determine the value for money to the English National Health Service (NHS) of adding AAP to SOC. We used a decision analytic model to evaluate cost-effectiveness of providing AAP in the English NHS. Between 2011–2014, the STAMPEDE trial recruited 1917 men with high-risk localised, locally advanced, recurrent or metastatic PC starting first-line androgen-deprivation therapy (ADT), and they were randomised to receive SOC plus AAP, or SOC alone. Lifetime costs and quality-adjusted life-years (QALYs) were estimated using STAMPEDE trial data supplemented with literature data where necessary, adjusting for baseline patient and disease characteristics. British National Formulary (BNF) prices (£98/day) were applied for AAP. Costs and outcomes were discounted at 3.5%/year. AAP was not cost-effective. The incremental cost-effectiveness ratio (ICER) was £149,748/QALY gained in the non-metastatic (M0) subgroup, with 2.4% probability of being cost-effective at NICE’s £30,000/QALY threshold; and the metastatic (M1) subgroup had an ICER of £47,503/QALY gained, with 12.0% probability of being cost-effective. Scenario analysis suggested AAP could be cost-effective in M1 patients if priced below £62/day, or below £28/day in the M0 subgroup. AAP could dominate SOC in the M0 subgroup with price below £11/day. AAP is effective for non-metastatic and metastatic disease but is not cost-effective when using the BNF price. AAP currently only has UK approval for use in a subset of M1 patients. The actual price currently paid by the English NHS for abiraterone acetate is unknown. Broadening AAP’s indication and having a daily cost below the thresholds described above is recommended, given AAP improves survival in both subgroups and its cost-saving potential in M0 subgroup.